Engineered cells and methods for the synthesis of caffeoyltyramine and feruloyltyramine

Abstract

Disclosed herein are recombinant host cells and methods of culturing the recombinant host cells to produce high titers of tyramine hydroxycinnamic acid amides, including caffeoyltyramine and feruloyltyramine. Additionally, disclosed herein are mutagenized enzymes with coumaroyltyramine 3-hydroxylase activity.

Description

[0001]PATENT APPLICATION DOCKET NO. CELB-010-W01 ENGINEERED CELLS AND METHODS FOR THE SYNTHESIS OF CAFFEOYLTYRAMINE AND FERULOYLTYRAMINE RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 625,909, filed on January 26, 2024, the entire teachings of which are incorporated herein by reference. STATEMENT REGARDING SEQUENCE LISTING The Sequence Listing associated with this application is provided in xml format in lieu of a paper copy and is hereby incorporated by reference into the Specification. The name of the file containing the Sequence Listing is CELB-010-WO1_SEQLISTING.xml. The xml file is 87,802 bytes, was created on January 24, 2025, and is being submitted electronically via Patent Center. BACKGROUND OF THE INVENTION Tyramine hydroxycinnamic acid amides are produced by plants and are commonly associated with cell wall tissues near pathogen infected or wound healing regions. Their presence is thought to create a barrier to pathogens by reducing cell wall digestibility, so they are associated with pathogen defense from plants. In recent studies, caffeoyltyramine (CT), feruloyltyramine (FT), and derivatives thereof, were shown to have potent biological activities with therapeutic implications. For example, N-trans- caffeoyl tyramine and dihydro-N-caffeoyltyramine were demonstrated in multiple studies to inhibit COX-2 expression and to modulate inflammation resulting in suppressed production of prostaglandin E2, nitric oxide, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin 10 (IL-10). In another study, CT was also shown to protect cells from oxidative damage from hydrogen peroxide by increasing the activity of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). In a recent study of {M0540533.1 } CELB-010-W01 -2- neuroprotective effects of amide alkaloids Bassia indica, FT was demonstrated to inhibit β-secretase, monoamine oxidase enzymes, phosphorylated tau protein along with possessing anti-aggregation activity against amyloid-β peptides. Additionally, CT and FT were recently demonstrated as strong HNF4a agonists, which act to control the level of fat storage in the liver by inducing fat clearance. In other studies, it was shown that HNF4a controls genes that are important for inflammatory bowel disease and Paneth cells and that CT reversed the loss of Paneth cell markers that occurred in high fat diet in mice. When taken together, these studies show strong evidence that CT, FT, and derivatives thereof have therapeutic potential for treating acute or chronic inflammation, oxidative stress mediated diseases and disorders, fatty liver disease, and are neuroprotective, and therefore could beneficially be formulated as food supplements or pharmaceutical formulations to meet these needs. Isolation of CT and FT from plants presents one option to produce high-purity CT and FT. Reliance on CT and FT derived from plants, however, has numerous disadvantages. These disadvantages include high cost, presence of undesired impurities, limitations in raw ingredient sourcing and susceptibility to supply chain disruptions. An alternative source for their synthesis and manufacturing is therefore required. A fermentation or bioconversion process will be most appropriate to synthesize CT and FT in a green and cost-effective way, while minimizing or eliminating undesired impurities, supply chain disruptions and raw ingredient sourcing limitations. The key enzymes in their synthesis include hydroxycinnamoyl-CoA ligase (HCL) and tyramine-N- hydroxycinnamoyl-CoA transferase (THT). While enzymes that perform the exact reactions, or the same reactions on similar substrates, of the CT and FT biosynthesis pathways are known, only small amounts of tyramine-N-hydroxycinnamic acid amides, such as 190-500 mg / L of coumaroyltyramine (CmT), have been produced in examples where HCL and THT were expressed in E. coli with glucose supplementation. These methods relied on the synthesis of both coumaric acid (CmA) and tyramine (TyM) from tyrosine (Tyr) using tyrosine ammonia lyase (TAL) and tyrosine decarboxylase (TDC), respectively. Thus, more robust and efficient fermentative methods are required to economically produce CT, FT, and their derivatives. 4904-4134-6834, v.1 CELB-010-W01 -3- SUMMARY OF THE INVENTION Described herein are engineered recombinant host cells and methods of their culture that produce high titers (>4 g / L) of tyramine hydroxycinnamic acid amides, CmT, CT, and FT, either from a combination of glucose and CmA, caffeic acid (CA), or ferulic acid (FA) feeds, or from glucose alone. Also disclosed herein are modified enzymes which increase the titer of tyramine hydroxycinnamic acid amides from a given amount of glucose in the presence or absence of CmA, CA, and / or FA feeds. Thus, provided are engineered recombinant host cells, methods of their culture, and modified enzymes which solve the problems of the prior art, to efficiently obtain high titers of tyramine hydroxycinnamic acid amides. Some aspects of the present disclosure are directed to a recombinant host cell metabolically engineered to produce an increased yield of tyramine hydroxycinnamic acid amides from at least one aldohexose, ketohexose, or aldopentose substrate, wherein the cell comprises: nucleic acids which encode a tyrosine decarboxylase (TDC) enzyme (E.C. 4.1.1.25); nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); nucleic acids which encode enzymes of the tyrosine biosynthesis pathway and tyrosine precursor metabolite biosynthesis pathways to enable production of sufficient quantities of tyrosine to support increased yield of tyramine hydroxycinnamic acid amide synthesis from the at least one aldohexose, ketohexose, or aldopentose substrate; optionally, nucleic acids which encode a coumaroyltyramine-3-hydroxylase enzyme (CmT3H); and optionally, nucleic acids which encode an O-methyltransferase enzyme, capable of transferring a methyl group to the O3’ of caffeoyltyramine; 4904-4134-6834, v.1 CELB-010-W01 -4- wherein the TDC selectively tyrosine over phenylalanine and / or the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid. In some embodiments, the at least one aldohexose, ketohexose, or aldopentose substrate is selected from the group consisting of glucose, mannose, galactose, fructose, D-xylose, and L-arabinose. In some embodiments, wherein the aldohexose is glucose. In some embodiments, the recombinant host cell further comprises: nucleic acids which encode enzymes of the phenylalanine biosynthesis pathway and phenylalanine precursor biosynthesis pathways to enable production of sufficient quantities of phenylalanine to support increased yield of hydroxycinnamic tyramine amide synthesis from at least one aldohexose, ketohexose, or aldopentose substrate; nucleic acids which encode a phenylalanine ammonia lyase enzyme (PAL) (E.C. 4.3.1.24, 4.3.1.25), and nucleic acids which encode a cinnamate 4-monooxygenase enzyme (C4H) (E.C. 1.14.14.91); optionally, nucleic acids which encode a 4-coumarate 3-hydroxylase enzyme (C3H), capable of adding a hydroxyl group to the C3’ of coumaric acid and / or coumaroyl-CoA; and optionally, nucleic acids which encode an O-methyltransferase, capable of selectively transferring a methyl group to the O3’ of caffeic acid and / or caffeoyl-CoA rather than the O4’ of caffeic acid and / or caffeoyl-CoA. In some embodiments, the TDC has an amino acid sequence with at least 85% identity to the amino acid sequence of TDC1 (SEQ ID NO: 1), TDC5 (SEQ ID NO: 2), TDC7 (SEQ ID NO: 3), TDC8 (SEQ ID NO: 4), or TDC9 (SEQ ID NO: 5), and wherein the TDC selectively decarboxylates tyrosine over phenylalanine. In some embodiments, the TDC has an amino acid sequence with at least 90% identity to the amino acid sequence of TDC7 (SEQ ID NO: 3). In some embodiments, the HCL has an amino acid sequence with at least 85% identity to the amino acid sequence of HCL1 (SEQ ID NO: 6), HCL2 (SEQ ID NO: 7), HCL3 (SEQ ID NO: 8), HCL7 (SEQ ID NO: 9), HCL8 (SEQ ID NO: 10), HCL9 (SEQ ID NO: 11), HCL11 (SEQ ID NO: 12), HCL12 (SEQ ID NO: 13), HCL13 (SEQ ID NO: 4904-4134-6834, v.1 CELB-010-W01 -5- 14), HCL14 (SEQ ID NO: 15), HCL15 (SEQ NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18) or HCL18 (SEQ ID NO: 19). In some embodiments, the HCL has an amino acid sequence with at least 90% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19), and wherein the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid. In some embodiments, the THT has an amino acid sequence with 85% identity to the amino acid sequence of THT1 (SEQ ID NO: 20), THT2 (SEQ ID NO: 21), THT3 (SEQ ID NO: 22), THT17 (SEQ ID NO: 23), THT18 (SEQ ID NO: 24), THT19 (SEQ ID NO: 25), THT20 (SEQ ID NO: 26), THT22 (SEQ ID NO: 27), THT23 (SEQ ID NO: 28), THT24 (SEQ ID NO: 29), THT25 (SEQ ID NO: 30), THT26 (SEQ ID NO: 31), THT27 (SEQ ID NO: 32), THT31 (SEQ ID NO: 33), or THT32 (SEQ ID NO: 34). In some embodiments, the CmT3H is present and comprises an amino acid sequence with at least 80% identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the recombinant host cell further comprises nucleic acids which encode one or more NADPH-cytochrome P450 reductases (CPR). In some embodiments, the one or more CPRs comprise an amino acid sequence with at least 90% identity to the amino acid sequence of AtATR2 (SEQ ID NO: 36), AmCPR1 (SEQ ID NO: 37), and AmCPR2 (SEQ ID NO: 38). In some embodiments, the CmT3H is present and comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared to caffeoyltyramine yields obtained in a recombinant host cell expressing the polypeptide of SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid 4904-4134-6834, v.1 CELB-010-W01 -6- sequence of SEQ ID NO: 35. In some the at least one amino acid modification comprises at least two and up to twenty amino acid modifications. In some embodiments, a recombinant host cell as described herein, wherein at least one O-methyltransferase is present and comprises an amino acid sequence with at least 85% identity to the amino acid sequence of OMT6 (SEQ ID NO: 39), OMT7 (SEQ ID NO: 40), OMT8 (SEQ ID NO: 41), OMT9 (SEQ ID NO: 42), or OMT10 (SEQ ID NO: 43), wherein the at least one O-methyltransferase is capable of selectively transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine, rather than the O4’ of caffeic acid, caffeoyl-CoA and / or caffeoyltyramine. In some embodiments, the PAL comprises an amino acid sequence with at least 85% identity to the amino acid sequence of AML1 (SEQ ID NO: 44). In some embodiments, the C4H comprises an amino acid sequence with at least 85% identity to the amino acid sequence of SEQ ID NO: 45. In some embodiments, wherein the HCL comprise a first domain comprising the amino acid sequence TAXGL, and a second domain comprising the amino acid sequence IQSDPITSXIK, wherein X in both amino acid sequences signify any amino acid. In some embodiments, a recombinant host cell as described herein, wherein the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolites through at least one aromatic amino acid precursor metabolite biosynthesis pathway and / or wherein the cell has been engineered to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways. In some embodiments, the increased flux through an aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway. In some embodiments, the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D-erythrose-4-phosphate, and chorismate. In some embodiments, the aromatic amino acid precursor metabolite 4904-4134-6834, v.1 CELB-010-W01 -7- pathway enzyme is an enzyme of the pentose pathway, the glycolysis pathway, or the shikimate pathway. In some embodiments, the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 90% identity to YlAro4 (SEQ ID NO: 46). In some embodiments, the recombinant host cell expresses a feedback resistant ARO4 enzyme. In some embodiments, the feedback resistant ARO4 enzyme comprises a substitution comprising K221L. In some embodiments, the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is selected from ARO1, chorismite synthase, chorismite mutase, prephenate dehydrogenase, and hydroxyphenylpyruvate aminotransferase. In some embodiments, the Aro1 enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47). In some embodiments, the chorismite synthase enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of ChS (SEQ ID NO: 48). In some embodiments, the chorismite mutase enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of ChM (SEQ ID NO: 49). In some embodiments, the prephenate dehydrogenase enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51). In some embodiments, a recombinant host cell as described herein, wherein the recombinant host cell is a fungal cell, an algal or protist cell, a plant cell, or a bacterial cell. In some embodiments, the fungal cell is a yeast cell selected from the group consisting of Yarrowia, Saccharomyces, Candida, Ashbya, Cyberlindnea, Kluveromyces, Arxula, Xanthophyllomyces, Schizosaccharomyces, Hansenula, Xanthophyllomyces, Lypomyces, Rhodotorula, Rhodosporidiumm, Candida, Cryptococcus or Pichia. In some embodiments, the yeast cell is Yarrowia. In some embodiments, the fungal cell is a Mucor, Mortierella, Fusarium, Sarocladium, Trichosporon or Aspergillus. In some embodiments the algal or protist cell is a Thraustochytrium, Schizochytrium, Aurantiochytrium, Chlorella, Auxenochlorella, Nannochloropsis, Scenedesmus, Tetraselmis, Botryococcus, or Chlamydomonas. In some embodiments, the plant cell is 4904-4134-6834, v.1 CELB-010-W01 -8- Arabidopsis, Artemisia, Bambusoideae, Glycine, Medicago, Nicotiana, Oryza, Oryzoideae, Phyllostachys, Physcomitrella, Pooideae, Silybum, Solanum, Taxus, or Vitis vinifera. In some embodiments the bacterial cell is a Rhodococcus or Gordonia. In some embodiments, a recombinant host cell as described herein, wherein the recombinant host cell has been engineered to inactivate or reduce expression of genes which encode at least one enzyme that catalyzes production of byproducts which reduce the yield of coumaroyltyramine, caffeoyltyramine, and / or feruloyltyramine. In some embodiments, the recombinant host cell is engineered to inactivate or reduce expression of a native double bond reductase which acts on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof, and the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof. In some embodiments, the double bond reductase which is inactivated is DBR (SEQ ID NO: 52) or homologs thereof that act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof. In some embodiments, the nucleic acids encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 95% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54). In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of polypeptide with tyramine monoamine oxidase activity. In some embodiments, the polypeptide with tyramine monoamine oxidase activity is MAO3 (SEQ ID NO 55), or a homolog thereof. In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with O4’- methyltransferase activity. In some embodiments, the polypeptide with O4’- methyltransferase activity is OMT1 (SEQ ID NO: 56), or homologs thereof that have O4’-methyltrasnferase activity. In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with tyramine acetylase activity. In some embodiments, the polypeptide with tyramine acetylase activity is classified in E.C. 2.3.1.87 or contains the IPR000182 motif, and possesses tyramine 4904-4134-6834, v.1 CELB-010-W01 -9- acetylase activity. In some embodiments, the with tyramine acetylase activity is HAT1 (SEQ ID NO: 57), or homologs thereof which possess tyramine acetylase activity. In some embodiments, the recombinant host cell has been engineered to inactivate or disrupt expression of a polypeptide with ATP-citrate lyase activity. In some embodiments, the polypeptide with ATP-citrate lyase activity is ACL1 (SEQ ID NO: 63), or homologs thereof that possess ATP-citrate lyase activity. In some embodiments, a recombinant host cell as described herein, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid or ferulic acid from a culture medium. In some embodiments, the one or more transporters comprise polypeptides with an amino acid sequence with at least 85% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62). Some aspects of the present disclosure are directed to a cell culture, comprising recombinant host cells as described herein, the cell culture further comprising: a nutrient medium comprising an aldohexose, ketohexose, or aldopentose substrate, wherein the nutrient medium further comprises a buffer, a nitrogen source, amino acids, a pH adjuster, vitamins, minerals, an antibiotic, and / or a cell extract; and tyramine hydroxycinnamic acid amides produced by the recombinant host cells, wherein the tyramine hydroxycinnamic acid amides are present in an amount of at least 3 g / L. In some embodiments, the aldohexose substrate is glucose. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 5 g / L, wherein the cell culture does not comprise exogenous coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid, and wherein the tyramine hydroxycinnamic acid amides were produced by the recombinant host cells without addition of supplemental coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid. In some embodiments, the nutrient medium further comprises one or more of coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, and ferulic acid. In 4904-4134-6834, v.1 CELB-010-W01 -10- some embodiments, the tyramine acid amides produced by the recombinant host cell are present in an amount of at least 10 g / L. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise feruloyltyramine in at least 15 g / L. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise caffeoyltyramine in at least 12 g / L. In some embodiments, the cell culture comprises caffeic acid or ferulic acid, and wherein a portion of the caffeic acid or ferulic acid present is exogenous, not having been produced by the recombinant host cell. In some embodiments, the recombinant host cell comprises nucleic acids which encode a transporter protein that increases uptake of coumaric acid, caffeic acid or ferulic acid, from a culture medium, and wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 10 g / L. In some embodiments, the tyramine hydroxycinnamic acid amides were produced by the recombinant host cell in a week or less, five days or less, or three days or less. Some aspects of the present disclosure are directed to a method of producing tyramine hydroxycinnamic acid amides comprising: culturing a recombinant host cell in the presence of an aldohexose, ketohexose, or aldopentose substrate for a period of time, wherein the recombinant host cell is metabolically engineered to produce an increased yield of tyramine hydroxycinnamic acid amides from at least one aldohexose, ketohexose, or aldopentose substrate, wherein the recombinant host cell comprises: nucleic acids which encode a tyrosine decarboxylase (TDC) enzyme (E.C. 4.1.1.25); nucleic acids which encode a hydroxycinnamoyl / 4-coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); nucleic acids which encode enzymes of the tyrosine biosynthesis pathway and tyrosine precursor biosynthesis pathways to enable production of sufficient quantities of tyrosine to support increased yield of tyramine and tyramine hydroxycinnamic acid 4904-4134-6834, v.1 CELB-010-W01 -11- amide synthesis from the at least one ketohexose, or aldopentose substrate; and optionally, nucleic acids which encode a coumaroyltyramine-3-hydroxylase enzyme (CmT3H); optionally, nucleic acids which encode an O-methyltransferase enzyme, capable of transferring a methyl group to the O3’ of caffeoyltyramine; wherein the TDC selectively decarboxylates tyrosine over phenylalanine and / or the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid; thereby producing tyramine hydroxycinnamic acid amides. In some embodiments, the at least one aldohexose, ketohexose, or aldopentose substrate is selected from the group consisting of glucose, mannose, galactose, fructose, D-xylose, glycerol and L-arabinose. In some embodiments, the aldohexose is glucose. In some embodiments, the recombinant host cell is cultured in the presence of one or more of coumaric acid, caffeic acid or ferulic acid. In some embodiments, the recombinant host cell is cultured in the presence of glucose and one or both of caffeic acid and ferulic acid. In some embodiments, the method further comprises isolating and purifying the tyramine hydroxycinnamic acid amides produced by the recombinant host cell. In some embodiments, the recombinant host cell further comprises: nucleic acids which encode enzymes of the phenylalanine biosynthesis pathway and phenylalanine precursor biosynthesis pathways to enable production of sufficient quantities of phenylalanine to support increased yield of hydroxycinnamic tyramine amide synthesis from at least one aldohexose, ketohexose, or aldopentose substrate; nucleic acids which encode a phenylalanine ammonia lyase enzyme (PAL) (E.C. 4.3.1.24, 4.3.1.25) and nucleic acids which encode a cinnamate 4-monooxygenase enzyme (C4H) (E.C. 1.14.14.91); optionally, nucleic acids which encode a 4-coumarate 3-hydroxylase (C3H), capable of adding a hydroxyl group to the C3’ of coumaric acid, coumaroyl-CoA, and / or coumaroyltyramine; and 4904-4134-6834, v.1 CELB-010-W01 -12- optionally, nucleic acids which O-methyltransferase , capable of transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine. In some embodiments, the TDC has an amino acid sequence with at least 85% identity to the amino acid sequence of TDC1 (SEQ ID NO: 1), TDC5 (SEQ ID NO: 2), TDC7 (SEQ ID NO: 3), TDC8 (SEQ ID NO: 4), or TDC9 (SEQ ID NO: 5), and wherein the TDC selectively decarboxylates tyrosine over phenylalanine. In some embodiments, the TDC has an amino acid sequence with at least 90% identity to the amino acid sequence of TDC7 (SEQ ID NO: 3). In some embodiments, the HCL has an amino acid sequence with at least 85% identity to the amino acid sequence of sequence of HCL1 (SEQ ID NO: 6), HCL2 (SEQ ID NO: 7), HCL3 (SEQ ID NO: 8), HCL7 (SEQ ID NO: 9), HCL8 (SEQ ID NO: 10), HCL9 (SEQ ID NO: 11), HCL11 (SEQ ID NO: 12), HCL12 (SEQ ID NO: 13), HCL13 (SEQ ID NO: 14), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), and HCL18 (SEQ ID NO: 19). In some embodiments, the HCL has an amino acid sequence with at least 90% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19), and wherein the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid. In some embodiments, the THT has an amino acid sequence with 85% identity to the amino acid sequence of THT1 (SEQ ID NO: 20), THT2 (SEQ ID NO: 21), THT3 (SEQ ID NO: 22), THT17 (SEQ ID NO: 23), THT18 (SEQ ID NO: 24), THT19 (SEQ ID NO: 25), THT20 (SEQ ID NO: 26), THT22 (SEQ ID NO: 27), THT23 (SEQ ID NO: 28), THT24 (SEQ ID NO: 29), THT25 (SEQ ID NO: 30), THT26 (SEQ ID NO: 31), THT27 (SEQ ID NO: 32), THT31 (SEQ ID NO: 33), or THT32 (SEQ ID NO: 34). In some embodiments, the CmT3H is present and comprises an amino acid sequence with at least 80% to the amino acid sequence of SEQ ID NO:35. In some embodiments, the recombinant host cell further comprises nucleic acids which encode one or more NADPH-cytochrome P450 reductases (CPR). In some 4904-4134-6834, v.1 CELB-010-W01 -13- embodiments, the one or more CPRs amino acid sequence with at least 85% identity to the amino acid sequence of AtATR2 (SEQ ID NO: 36), AmCPR1 (SEQ ID NO: 37), and AmCPR2 (SEQ ID NO: 38). In some embodiments, the CmT3H is present and comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared with caffeoyltyramine yields obtained in a recombinant host cell expressing SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least two and up to twenty amino acid modifications. In some embodiments, the at least one O-methyltransferase is present and comprises an amino acid sequence with at least 85% identity to the amino acid sequence of OMT6 (SEQ ID NO: 39), OMT7 (SEQ ID NO: 40), OMT8 (SEQ ID NO: 41), OMT9 (SEQ ID NO: 42), or OMT10 (SEQ ID NO: 43), wherein the at least one O- methyltransferase is capable of transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine. In some embodiments, the at least one O- methyltransferase provides enhanced yield of feruloyltyramine and comprises an amino acid sequence with at least 85% identity to the amino acid sequence of OMT9 (SEQ ID NO: 42). In some embodiments, the PAL comprises an amino acid sequence with at least 85% identity to the amino acid sequence of AML1 (SEQ ID NO: 44). In some embodiments, the C4H comprises an amino acid sequence with at least 85% identity to the amino acid sequence of SEQ ID NO: 45. In some embodiments, the HCL comprise a first domain comprising the amino acid sequence TAXGL, and a second domain 4904-4134-6834, v.1 CELB-010-W01 -14- comprising the amino acid sequence wherein X in both amino acid sequences signify any amino acid. In some embodiments, the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolite through at least one aromatic amino acid precursor biosynthesis pathway and / or wherein the cell has been engineered to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways. In some embodiments, the increased flux through an aromatic amino acid precursor pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway. In some embodiments, the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D-erythrose-4-phosphate, and chorismate. In some embodiments, wherein the aromatic amino acid precursor pathway enzyme is an enzyme of the pentose phosphate pathway, the glycolysis pathway, and the shikimate pathway. In some embodiments, the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 90% identity to YlAro4 (SEQ ID NO: 46). In some embodiments, the recombinant host cell expresses a feedback resistant ARO4 enzyme. In some embodiments, the feedback resistant ARO4 enzyme comprises a substitution comprising K221L. In some embodiments, the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is selected from ARO1, chorismite synthase, chorismite mutase, prephenate dehydrogenase, and hydroxyphenylpyruvate aminotransferase. In some embodiments, the Aro1 enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47). In some embodiments, the chorismite synthase enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of ChS (SEQ ID NO: 48). In some embodiments, the chorismite mutase enzyme comprises an amino acid sequence with at least 95% identity to the amino acid sequence of ChM (SEQ ID NO: 49). In some embodiments, the prephenate dehydrogenase enzyme 4904-4134-6834, v.1 CELB-010-W01 -15- comprises an amino acid sequence with at identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51). In some embodiments, the recombinant host cell is a yeast cell, an algal or protist cell, or a bacterial cell. In some embodiments, yeast cell is Yarrowia, Saccharomyces, Candida, Ashbya, Cyberlindnea, Kluveromyces, Arxula, Xanthophyllomyces, Schizosaccharomyces, Hansenula, Xanthophyllomyces, or Pichia. In some embodiments, wherein the yeast cell is Yarrowia. In some embodiments, the recombinant host cell has been engineered to inactivate or disrupt expression of genes which encode at least one enzyme that catalyzes production of byproducts which reduce the yield of coumaroyltyramine, caffeoyltyramine, and / or feruloyltyramine. In some embodiments, the recombinant host cell is engineered to inactivate or reduce expression of a native double bond reductase which acts on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof, and the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl- CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof. In some embodiments, the double bond reductase which is inactivated is DBR (SEQ ID NO: 52), or homologs thereof that act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-COA derivatives thereof. In some embodiments, the recombinant host cell further comprises nucleic acids that encode an exogenous enoyl- CoA reductase enzyme with an amino acid sequence with 95% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54). In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of polypeptide with tyramine monoamine oxidase activity. In some embodiments, the polypeptide with tyramine monoamine oxidase activity is MAO3 (SEQ ID NO: 55), or a homolog thereof. In some embodiments, the recombinant host cells has been engineered to inactivate or disrupt expression of a polypeptide with O4’- methyltransferase activity. In some embodiments, the polypeptide with O4’- methyltransferase activity is OMT1 (SEQ ID NO: 56), or homologs thereof that have O4’-methyltrasnferase activity. 4904-4134-6834, v.1 CELB-010-W01 -16- In some embodiments, the cell has been engineered to inactivate or reduce expression of a polypeptide with tyramine acetylase activity. In some embodiments, the polypeptide with tyramine acetylase activity is classified in E.C. 2.3.1.87 or contains the IPR000182 motif, and possess tyramine acetylase activity. In some embodiments, the polypeptide with tyramine acetylase activity is HAT1 (SEQ ID NO: 57), or homologs thereof which possess tyramine acetylase activity. In some embodiments, the recombinant host cells has been engineered to inactivate or disrupt expression of a polypeptide with ATP-citrate lyase activity. In some embodiments, the polypeptide with ATP-citrate lyase activity is ACL1 (SEQ ID NO: 63) , or homologs thereof that possess ATP-citrate lyase activity. In some embodiments, a method as described herein, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid, ferulic acid, coumaroyltyramine and / or caffeoyltyramine from a culture medium. In some embodiments, the one or more transporters comprise polypeptides with an amino acid sequence with at least 85% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62). Some aspects of the present disclosure are directed to a polypeptide with coumaroyltyramine 3-hydroxylase activity, wherein the polypeptide comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared with caffeoyltyramine yields obtained in a recombinant host cell expressing a polypeptide with an amino acid sequence of SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO: 35. In some 4904-4134-6834, v.1 CELB-010-W01 -17- embodiments, the at least one amino acid comprises at least two and up to twenty amino acid modifications. Some aspects of the present disclosure are directed to a preventing formation of acetyl tyramine in a recombinant host cell, the process comprising adding a bolus of >10 g / L of caffeic or ferulic acid to a fermenter containing the recombinant host cell, and subsequently maintaining the concentration of caffeic or ferulic acid at >0.05 g / L throughout the fermentation run, thereby preventing formation of acetyl tyramine in the recombinant host cell. Some aspects of the present disclosure are directed to a process for isolating and purifying caffeoyltyramine (CT) and / or feruloyltyramine (FT) produced from a recombinant host cell, the process comprising the steps of: 1) subjecting a fermentation broth containing the recombinant host cell along with the produced FT and / or CT to centrifugation to obtain a cell pellet; 2) adding alkaline water having a pH of 12.5-14 to the cell pellet to selectively redissolve the CT or FT, and removing solid cellular debris to obtain an alkaline solution comprising CT or FT; 3) acidifying the alkaline solution to a pH of 5 to 6.5 to precipitate CT or FT; and 4) subjecting the precipitated CT or FT to filtration to obtain isolated CT or FT. In some embodiments, the process further comprises the steps of: 5) redissolving the isolated CT or FT in ethanol; 6) filtering the ethanol solution to remove insoluble materials; 7) diluting the ethanol solution with 3-4 volumes of water to precipitate CT and FT; and 8) subjecting the precipitated CT or FT to filtration to obtain purified solid CT or FT. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention are further described by way of the following figures. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee. FIG. 1 depicts multiple pathways for the synthesis of coumaroyltyramine (CmT), caffeoyltyramine (CT), and feruloyltyramine (FT). 4904-4134-6834, v.1 CELB-010-W01 -18- FIG. 2 depicts a novel pathway for of CmT, CT, and FT from glucose. The depicted strain uses native biosynthetic pathway for the synthesis of tyrosine and phenylalanine and an engineered non-native pathway comprising tyrosine decarboxylase (TDC), phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), hydroxycinnamoyl / coumarate:CoA ligase (HCL), tyramine-N- hydroxycinnamoyl-CoA transferase (THT), CmT 3-hydroxylase (CmT3H), and O- methyltransferase (OMT). FIG. 3 depicts byproduct formation from cinnamic acids using native yeast and Y. lipolytica genes, wherein the byproducts are formed first by the double bond reductase (DBR), such as YlTSC13, and a subsequent byproduct may be formed by O3’- methyltransferase (OMT), such as by OMT1. FIG. 4 depicts the byproduct formation from tyramine involving a tyramine acetyl transferase (TAC) and monoamine oxidase (MAO), such as MAO3. FIG. 5 shows an alignment of the HCLs that do not act on cinnamic acid and a crystal structure model of HCL7 bound to coumaric acid. The boxes show the areas of the protein that is interacting with coumaric acid. DETAILED DESCRIPTION OF THE INVENTION Cells and cell culture Disclosed herein are engineered recombinant host cells which solve the problems of the prior art to produce high titers of tyramine hydroxycinnamic acid amides from at least one aldohexose, ketohexose, or aldopentose substrate. The selection of host cell is not particularly limited, so long as it is suitable for being engineered to inactivate genes which produce tyramine hydroxycinnamic acid amide byproducts or to possess genes which express enzymes essential to produce high titer of tyramine hydroxycinnamic acid amides. In some embodiments, the cell may be a microorganism or a plant. In some embodiments, the microorganism is a bacteria (e.g., E. coli), an algae or protist, or a fungi. In some embodiments, the fungi is an oleaginous yeast (e.g., a Yarrowia lipolytica strain). In some embodiments, the bacteria is Escherichia coli. 4904-4134-6834, v.1 CELB-010-W01 -19- Suitable cells may include, but are to, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha (now known as Pichia angusta), Kluyveromyces sp., Kluyveromyces lactis, Kluyveromyces marxianus, Schizosaccharomyces pompe, Dekkera bruxellensis, Arxula adeninivorans, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Neurospora crassa, Chlamydomonas reinhardtii, Cryptococcus liquefaciens, Cryptococcus neoformans, Cryptococcus gattii, Ashbya gossypii, Cyberlindnea jadinii, Kluyveromyces lactis, Kluyveromyces marxianus, Xanthophyllomyces dendrorhous, Lypomyces starkeyi, Rhodotuorula mucilaginosa, Rhodosporidium toruloides, Mucor circinelloides, Mucor lusitanicus, Mucor rouxii, Mortierella alpina, Mortierella elongate, Sarocladium schorii, Sarocladium oryzae, Sarocladium zeae, Sarocladium zeinab, Trichosporon asahii, Trichosporon adeninovorans, Aspergillus nidulans, Aspergillus oryzae, Aspergillus terreus, Aspergillus unguis, Thraustochytrium aureum, Thraustochytrium roseum, Schizochytrium ATCC 20888, Schizochytrium limacinum, Aurantiochytrium SK4, Aurantiochytrium SW1, Aurantiochytrium T66, Aurantiochytrtium limacinum, Chlorella ellipsoidea, Chlorella kessleri, Chlorella zofingiensis, Chlorella saccharaphila, Chlorella protothecoides, Auxenochlorella protothecoides, Nannochloropsis oceanica, Nannochloropsis salina, Scenedesmus almeriensis, Scenedesmus obliquus, Scenedesmus subspicatus, Tetraselmis suecica, Tetraselmis subcordiformis, Synechocystis PCC6803, Botryococcus braunii, Chlamydomonas reinhardtii, Chlamydomonas met1, Chlamydomonas UVM4, Yarrowia lipolytica, and the like. In some embodiments, the cell is a protease-deficient strain of Saccharomyces cerevisiae. In some embodiments, the cell is a eukaryotic cell other than a plant cell. In some embodiments, the cell is a plant cell. In some embodiments, the cell is a plant cell, where the plant cell is one that does not normally produce tyramine hydroxycinnamic acid amides. In some embodiments, the cell is Saccharomyces 4904-4134-6834, v.1 CELB-010-W01 -20- cerevisiae. In some embodiments, the cell is lipolytica. In some embodiments, the cell disclosed herein is cultured in vitro. In some embodiments, the cell is a prokaryotic cell. Suitable prokaryotic cells may include, but are not limited to, any of a variety of laboratory strains of Escherichia coli, Lactobacillus sp., Salmonella sp., Shigella sp., and the like. See, e.g., Carrier et al, (1992) J. Immunol. 148:1176-1181; U.S. Pat. No. 6,447,784; and Sizemore et al. (1995) Science 270:299-302. Examples of Salmonella strains which can be employed may include, but are not limited to, Salmonella typhi and S. typhimurium. Suitable Shigella strains may include, but are not limited to, Shigella flexneri, Shigella sonnei, and Shigella disenteriae. Typically, the laboratory strain is one that is non-pathogenic. Non-limiting examples of other suitable bacteria may include, but are not limited to, Bacillus subtilis, Corynebacteria glutamicum, Gordonia neofelifaecis, Gordonia rubripertincta, Gordonia amarae, Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas mevalonii, Rhodobacter sphaeroides, Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodococcus sp., and the like. As outlined in Figure 2, there are multiple pathways to the synthesis of coumaroyltyramine (CmT), caffeoyltyramine (CT), and feruloylturamine (FT) from at least one aldohexose, ketohexose, or aldopentose substrate. In one embodiment, coumaric acid (CmA) is made from phenylalanine (Phe) using phenylalanine ammonia lyase (PAL) and cinnamate 4-hydroxylase (C4H), while tyramine (TyM) is produced from tyrosine (Tyr) using tyrosine decarboxylase (TDC). Producing both Phe and Tyr from prephenate results in a better balance of the two components needed to make CmT: CA derived from Phe and TyM derived from Tyr. This objective requires that the recombinant host cell comprises intact aromatic amino acid pathways, such as phenylalanine and tyrosine biosynthesis pathways. In some embodiments, coumaroyltyramine (CmT) is obtained by the action of hydroxycinnamoyl / coumarate: CoA ligase on coumaric acid and co-enzyme A to form the intermediate coumaroyl-CoA which is subsequently condensed with TyM by tyramine-N-hydroxycinnamoyl-CoA transferase (THT). Caffeoyltyramine can be obtained by oxidation of coumaroyltyramine by coumaroyl-3-hydroxylase (CmT3H), while feruloyltyramine can be obtained from caffeoyltyramine through action of a 4904-4134-6834, v.1 CELB-010-W01 -21- O3’methyltransferase. If coumaric acid, or ferulic acid are added to the culture medium, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA may be produced directly from the exogenous acids and CoA with help of a HCL enzyme, thus bypassing the phenylalanine / tyrosine biosynthesis pathways. Nonetheless, in some embodiments, the recombinant host cell comprises nucleic acids which encode enzymes of the phenylalanine and tyrosine biosynthesis pathways to enable endogenous production of tyrosine, phenylalanine, as well as cinnamic acid, coumaric acid, caffeic acid and ferulic acid. With endogenous production of these metabolites intact, supplementation with caffeic acid and and / or ferulic acid feed acts to enhance titers of caffeoyltyramine and feruloyltyramine obtained from the recombinant host cell. Thus, in some embodiments, the recombinant host cell comprises nucleic acids which encode a tyrosine decarboxylase (TDC) enzyme (E.C. 4.1.1.25). In some embodiments, the TDC has an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of TDC1 (SEQ ID NO: 1), TDC5 (SEQ ID NO: 2), TDC7 (SEQ ID NO: 3), TDC8 (SEQ ID NO: 4), or TDC9 (SEQ ID NO: 5). In some embodiments, the TDC selectively decarboxylates tyrosine over phenylalanine. In some embodiments, the TDC has an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 4904-4134-6834, v.1 CELB-010-W01 -22- 99%, 99.25%, 99.5%, 99.75%, or 100% to the amino acid sequence of TDC7 (SEQ ID NO: 3). In some embodiments, the recombinant host cell comprises nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12). In some embodiments, the HCL has an amino acid sequence with at least at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of HCL1 (SEQ ID NO: 6), HCL2 (SEQ ID NO: 7), HCL3 (SEQ ID NO: 8), HCL7 (SEQ ID NO: 9), HCL8 (SEQ ID NO: 10), HCL9 (SEQ ID NO: 11), HCL11 (SEQ ID NO: 12), HCL12 (SEQ ID NO: 13), HCL13 (SEQ ID NO: 14), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18) or HCL18 (SEQ ID NO: 19). In some embodiments, the HCL selectively ligates CoA to one or more of 4- coumaric acid, caffeic acid, and ferulic acid over cinnamic acid. In some embodiments, the HCL has an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19). 4904-4134-6834, v.1 CELB-010-W01 -23- In some embodiments, the HCL a first domain comprising the amino acid sequence TAXGL, and a second domain comprising the amino acid sequence IQSDPITSXIK, wherein X in both amino acid sequences signify any amino acid. In some embodiments, the recombinant host cell comprises nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110). In some embodiments, the THT has an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of THT1 (SEQ ID NO: 20), THT2 (SEQ ID NO: 21), THT3 (SEQ ID NO: 22), THT17 (SEQ ID NO: 23), THT18 (SEQ ID NO: 24), THT19 (SEQ ID NO: 25), THT20 (SEQ ID NO: 26), THT22 (SEQ ID NO: 27), THT23 (SEQ ID NO: 28), THT24 (SEQ ID NO: 29), THT25 (SEQ ID NO: 30), THT26 (SEQ ID NO: 31), THT27 (SEQ ID NO: 32), THT31 (SEQ ID NO: 33), or THT32 (SEQ ID NO: 34). In some embodiments, the recombinant host cells comprise nucleic acids which encode enzymes of the tyrosine biosynthesis pathway to enable production of sufficient quantities of tyrosine to support increased yield of tyramine hydroxycinnamic acid amide synthesis from the at least one aldohexose, ketohexose, or aldopentose substrate. In some embodiments, the cell has been engineered to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways. In some embodiments, the increased flux through an aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway. 4904-4134-6834, v.1 CELB-010-W01 -24- In some embodiments, the at least of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is ARO1. In some embodiments, the Aro1 enzyme comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47), or homologs thereof. In some embodiments, the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is chorismite synthase. In some embodiments, the chorismite synthase enzyme comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of ChS (SEQ ID NO: 48), or homologs thereof. In some embodiments, the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is prephenate dehydrogenase. In some embodiments, the chorismite mutase enzyme comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 4904-4134-6834, v.1 CELB-010-W01 -25- 95%, 95.25%, 95.5%, 95.75%, 96%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of ChM (SEQ ID NO: 49), or homologs thereof. In some embodiments, the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is hydroxyphenylpyruvate aminotransferase. In some embodiments, the prephenate dehydrogenase enzyme comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51), or homologs thereof. In some embodiments, the recombinant host cell comprises nucleic acids which encode enzymes of tyrosine precursor metabolite biosynthesis pathways to enable production of sufficient quantities of tyrosine to support increased yield of tyramine hydroxycinnamic acid amide synthesis from the at least one aldohexose, ketohexose, or aldopentose substrate. In some embodiments, the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolites through at least one aromatic amino acid precursor metabolite biosynthesis pathway. In some embodiments, the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D-erythrose-4-phosphate, and chorismate. In some embodiments, the aromatic amino acid precursor metabolite pathway enzyme is an enzyme of the pentose phosphate pathway, the glycolysis pathway, or the shikimate pathway. In some embodiments, the recombinant host cell overexpresses a wild type ARO4 enzyme. In some embodiments, the overexpressed wild type ARO4 enzyme comprises an amino acid sequence with 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 4904-4134-6834, v.1 CELB-010-W01 -26- 65%, 66%, 67%, 68%, 69%, 70%, 71%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to YlAro4 (SEQ ID NO: 46). In some embodiments, the recombinant host cell expresses a feedback-resistant ARO4 enzyme. In some embodiments, the feedback resistant ARO4 enzyme comprises a substitution comprising K221L. In some embodiments, the feedback resistant ARO4 enzyme comprises a K221L substitution and comprises an amino acid sequence with 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the recombinant host cell comprises nucleic acids which encode a coumaroyltyramine-3-hydroxylase enzyme (CmT3H). In some embodiments, the CmT3H is present and comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the CmT3H comprises an amino acid sequence with less than 100%, 99.75%, 99.5%, 99.25%, 99%, 98.75%, 98.5%, 98.25%, 98%, 97.75%, 97.5%, 4904-4134-6834, v.1 CELB-010-W01 -27- 97.25%, 97%, 96.75%, 96.5%, 96.25%, 95.5%, 95.25%, 95%, 94.75%, 94.5%, 94.25%, 94%, 93.75%, 93.5%, 93.25%, 93%, 92.75%, 92.5%, 92.25%, 92%, 91.75%, 91.5%, 91.25%, 91%, 90.75%, 90.5%, 90.25%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71%, 70%, 69%, 68%, 67%, 66%, or 65% identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the CmT3H is present and comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared to caffeoyltyramine yields obtained in a recombinant host cell expressing the polypeptide of SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO: 35. In some embodiments, the at least one amino acid modification comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acid modifications. In some embodiments, the amino acid modification comprises less than 20, less than 19, less than 18, less than 17, less than 16, less than 15, less than 14, less than 13, less than 12, less than 11, less than 10, less than 9, less than 8, less than 7, less than 6, less than 5, less than 4, or less than 3 amino acid modifications. In some embodiments, the amino acid modifications may be conservative amino acid substitutions or non-conservative amino acid substitutions. A conservative replacement (also called a conservative mutation, a conservative substitution or a conservative variation) is an amino acid replacement in a protein that changes a given amino acid to a different amino acid with similar biochemical properties (e.g., charge, 4904-4134-6834, v.1 CELB-010-W01 -28- hydrophobicity and size). As used herein, variations” refer to the replacement of an amino acid residue by another, biologically similar residue. Examples of conservative variations include the substitution of one hydrophobic residue such as isoleucine, valine, leucine or methionine for another; or the substitution of one polar residue for another, such as the substitution of arginine for lysine, glutamic for aspartic acids, or glutamine for asparagine, and the like. Other illustrative examples of conservative substitutions include the changes of: alanine to serine; arginine to lysine; asparagine to glutamine or histidine; aspartate to glutamate; cysteine to serine; glutamine to asparagine; glutamate to aspartate; glycine to proline; histidine to asparagine or glutamine; isoleucine to leucine or valine; leucine to valine or isoleucine; lysine to arginine, glutamine, or glutamate; methionine to leucine or isoleucine; phenylalanine to tyrosine, leucine or methionine; serine to threonine; threonine to serine; tryptophan to tyrosine; tyrosine to tryptophan or phenylalanine; valine to isoleucine or leucine, and the like. In some embodiments, the recombinant host cell comprises nucleic acids which encode an O-methyltransferase enzyme, capable of transferring a methyl group to the O3’ of caffeoyltyramine. In some embodiments, at least one O-methyltransferase is present and comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of OMT6 (SEQ ID NO: 39), OMT7 (SEQ ID NO: 40), OMT8 (SEQ ID NO: 41), OMT9 (SEQ ID NO: 42), or OMT10 (SEQ ID NO: 43). In some embodiments, the at least one O-methyltransferase is capable of selectively transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine, rather than the O4’ of caffeic acid, caffeoyl-CoA and / or caffeoyltyramine. 4904-4134-6834, v.1 CELB-010-W01 -29- In some embodiments, the cell comprises nucleic acids which encode a phenylalanine ammonia lyase enzyme (PAL) (E.C. 4.3.1.24, 4.3.1.25). In some embodiments, the PAL comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of AML1 (SEQ ID NO: 44). In some embodiments, the recombinant host cell comprises nucleic acids which encode a cinnamate 4-monooxygenase enzyme (C4H) (E.C. 1.14.14.91). In some embodiments, the C4H comprises an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of SEQ ID NO: 45. In some embodiments, the recombinant host cell comprises nucleic acids which encode a 4-coumarate 3-hydroxylase enzyme (C3H). In some embodiments, the C3H enzyme is capable of adding a hydroxyl group to the C3’ of coumaric acid and / or coumaroyl-CoA. In some embodiments, the recombinant host cell further comprises nucleic acids which encode one or more NADPH-cytochrome P450 reductases (CPR). In some embodiments, the one or more CPRs comprise an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 4904-4134-6834, v.1 CELB-010-W01 -30- 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of AtATR2 (SEQ ID NO: 36), AmCPR1 (SEQ ID NO: 37), and AmCPR2 (SEQ ID NO: 38). As shown in Figures 3 and 4, there are multiple byproducts produced by several enzymes which reduce the yield of caffeoyltyramine and feruloyltyramine. Thus, in some embodiments, the cell has been modified to knockdown expression of one or more genes that encode enzymes which produce unwanted byproducts in the biosynthesis pathways leading to the production of tyramine hydroxycinnamic acid amides and analogs thereof. In some embodiments the cell has been modified to knockout one or more genes that produce unwanted byproducts in the tyramine hydroxycinnamic acid amide biosynthesis pathway. It will be appreciated that the strategy to select knockdown or knockout of any one or more genes will depend on whether the gene-encoded product is critical for the survival of the cell, and the resulting increase in tyramine hydroxycinnamic acid amide yield obtained by the gene knockdown or knockout. In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of genes which encode at least one enzyme that catalyzes production of byproducts which reduce the yield of coumaroyltyramine, caffeoyltyramine, and / or feruloyltyramine. In some embodiments, the recombinant host cell is engineered to inactivate or reduce expression of a native double bond reductase which acts on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof, and the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl- CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof. In some embodiments, the double bond reductase which is inactivated is a polypeptide that has at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 4904-4134-6834, v.1 CELB-010-W01 -31- 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of DBR (SEQ ID NO: 52) or homologs thereof that act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof. In order to preserve vital pathways to the survival of the recombinant host cell, the recombinant host cell can be engineered to express an exogenous enoyl-CoA reductase enzyme that does not act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, or feruloyl-CoA. In some embodiments, the recombinant host cell comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54). In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of polypeptide with tyramine monoamine oxidase activity. In some embodiments, the polypeptide with tyramine monoamine oxidase activity is a polypeptide with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of MAO3 (SEQ ID NO 55), or a homolog thereof. 4904-4134-6834, v.1 CELB-010-W01 -32- In some embodiments, the cell has been engineered to inactivate or reduce expression of a polypeptide with O4’-methyltransferase activity. In some embodiments, the polypeptide with O4’-methyltransferase activity is a polypeptide comprising an amino acid sequence which has at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of OMT1 (SEQ ID NO: 56), or homologs thereof that have O4’-methyltrasnferase activity. In some embodiments, the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with tyramine acetylase activity. In some embodiments, the polypeptide with tyramine acetylase activity is classified in E.C. 2.3.1.87 or contains the Gcn5-related N-acetyltransferases (GNAT) domain (IPR000182 motif) and possesses tyramine acetylase activity. In some embodiments, the polypeptide with tyramine acetylase activity is a polypeptide comprising an amino acid sequence which has at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of HAT1 (SEQ ID NO: 57), or homologs thereof which possess tyramine acetylase activity. In some embodiments, the recombinant host cell has been engineered to inactivate or disrupt expression of a polypeptide with ATP-citrate lyase activity. In some embodiments, the polypeptide with ATP-citrate lyase activity is a polypeptide comprising 4904-4134-6834, v.1 CELB-010-W01 -33- an amino acid sequence which has at least 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity with the amino acid sequence of ACL1 (SEQ ID NO: 63), or homologs thereof that possess ATP-citrate lyase activity. In some embodiments, a recombinant host cell as described herein, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid or ferulic acid from a culture medium. In some embodiments, the one or more transporters comprise polypeptides with an amino acid sequence with at least 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 85.5%, 86%, 86.5%, 87%, 87.5%, 88%, 88.5%, 89%, 89.5%, 90%, 90.25%, 90.5%, 90.75%, 91%, 91.25%, 91.5%, 91.75%, 92%, 92.25%, 92.5%, 92.75%, 93%, 93.25%, 93.5%, 93.75%, 94%, 94.25%, 94.5%, 94.75%, 95%, 95.25%, 95.5%, 95.75%, 96%, 96.25%, 96.5%, 96.75%, 97%, 97.25%, 97.5%, 97.75%, 98%, 98.25%, 98.5%, 98.75%, 99%, 99.25%, 99.5%, 99.75%, or 100% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62). In some embodiments, the cell is a yeast cell, an algal cell, or a bacterial cell. In some embodiments, the yeast cell is Saccharomyces, Pichia, or Yarrowia. In some embodiments, the cell is capable of synthesizing coumaric acid, caffeic acid, and / or ferulic acid when tyrosine is present in the cell through endogenous production. In some embodiments, the cell is capable of producing cinnamic acid, coumaric acid, caffeic acid, or ferulic acid when phenylalanine is present in the cell through endogenous production. 4904-4134-6834, v.1 CELB-010-W01 -34- In some embodiments, production of hydroxycinnamic acid amides in the cell is dependent on, or is enhanced by supplementation of cinnamic acid, coumaric acid, caffeic acid and / or ferulic acid within the fermentation medium in which the cell is grown. In other embodiments the concentration of caffeic or ferulic acid is maintained during the fermentation above 0.05mM, above 0.08 mM, above 0.1 mM, above 0.15 mM, above 0.2 mM, or above 0.25mM to reduce the formation of byproducts such as acetyl- tyramine. In some embodiments, caffeic or ferulic acid is added to the fermentation medium in which the cell is grown in an initial bolus of >5 g / L, >7.5 g / L, >10 g / L, >12.5 g / L or more, or about 4 g / L, 4.5 g / L, 5 g / L, 5.5 g / L, 6 g / L, 6.5 g / L, 7 g / L, 7.5 g / L, 8 g / L, 8.5 g / L, 9 g / L, 9.5 g / L, 10 g / L, 10.5 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, about 4 g / L, or more. In some embodiments, after the initial bolus of caffeic or ferulic acid is added to the fermentation medium in which the cell is grown, caffeic or ferulic acid is maintained throughout fermentation in an amount of >0.015 g / L, >0.018 g / L, >0.02 g / L, >0.03 g / L, >0.04 g / L, >0.05 g / L, >0.06 g / L, >0.07 g / L, >0.08 g / L, >0.09 g / L, >0.1 g / L, >0.125 g / L, >0.15 g / L, >0.2 g / L, >0.3, >0.4 g / L, or >0.5 g / L, but less than 20 g / L. In some embodiments, the cell is capable of converting one or more of cinnamic acid to coumaric acid, coumaric acid to caffeic acid, and caffeic acid to ferulic acid. In some embodiments, the cell is capable of forming caffeoyl-CoA from caffeic acid and Co-enzyme A. In some embodiments, the cell is capable of forming feruloyl-CoA from ferulic acid and Co-enzyme A. An expression vector or vectors can be constructed to include exogenous nucleotide sequences coding for an enzyme of the pentose phosphate pathway, glycolysis pathway, shikimate pathway, phenylalanine and / or tyrosine pathway, or tyramine hydroxycinnamic acid amide biosynthesis pathway as described herein operably linked to expression control sequences functional in the cell. Expression vectors applicable include, for example, plasmids, phage vectors, viral vectors, episomes and artificial chromosomes, including vectors and selection sequences or markers operable for stable integration into a host chromosome. Additionally, the expression vectors can include one or more selectable marker genes and appropriate expression control sequences. Selectable 4904-4134-6834, v.1 CELB-010-W01 -35- marker genes also can be included that, for provide resistance to antibiotics or toxins, complement auxotrophic deficiencies, or supply critical nutrients not in the culture media. Expression control sequences can include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like which are well known in the art. When two or more exogenous encoding nucleic acids are to be co- expressed, both nucleic acids can be inserted, for example, into a single expression vector or in separate expression vectors. For single vector expression, the encoding nucleic acids can be operationally linked to one common expression control sequence or linked to different expression control sequences, such as one inducible promoter and one constitutive promoter. The transformation of exogenous nucleic acid sequences can be confirmed using methods well known in the art. Such methods include, for example, nucleic acid analysis such as Northern blots or polymerase chain reaction (PCR) amplification of mRNA, or immunoblotting for expression of gene products, or other suitable analytical methods to test the expression of an introduced nucleic acid sequence or its corresponding gene product. It is understood by those skilled in the art that the exogenous nucleic acid is expressed in a sufficient amount to produce the desired product, and it is further understood that expression levels can be optimized to obtain sufficient expression using methods well known in the art and as disclosed herein. The term “exogenous” is intended to mean that the referenced molecule or the referenced activity is introduced into the cell. The molecule can be introduced, for example, by introduction of an encoding nucleic acid into the host genetic material such as by integration into a host chromosome or as non-chromosomal genetic material such as a plasmid. Therefore, the term as it is used in reference to expression of an encoding nucleic acid refers to introduction of the encoding nucleic acid in an expressible form into the cell. When used in reference to a biosynthetic activity, the term refers to an activity that is introduced into the host. The source can be, for example, a homologous or heterologous encoding nucleic acid that expresses the referenced activity following introduction into the cell. Therefore, the term “endogenous” refers to a referenced molecule or activity that is present in the cell. Similarly, the term when used in reference to expression of an encoding nucleic acid refers to expression of an encoding nucleic acid 4904-4134-6834, v.1 CELB-010-W01 -36- contained within the microbial organism. “heterologous” refers to a molecule or activity derived from a source other than the referenced species whereas “homologous” refers to a molecule or activity derived from the host microbial organism. Accordingly, exogenous expression of an encoding nucleic acid can utilize either or both a heterologous or homologous encoding nucleic acid. In some embodiments, the recombinant host cell is capable of making tyramine hydroxycinnamic acid amides or analogs thereof in the presence of a carbon source and, optionally, cinnamic acid, coumaric acid, caffeic acid and / or ferulic acid. Exemplary carbon sources include aldohexoses, ketohexoses and aldopentoses, as well as di- and oligo- saccharides comprising these monomers. In some embodiments, the aldohexoses, ketohexoses and aldopentoses, as well as disaccharides thereof comprise sucrose, glucose, mannitol, galactose, fructose, mannose, isomaltose, xylose, pannose, maltose, arabinose, cellobiose and 3-, 4-, or 5- oligomers thereof. In some embodiments, Other carbon sources include alcohol carbon sources such as, ethanol, and glycerol. Other carbon sources may contain a combination of the above carbon sources such as, for example, glucose / mannitol or glucose / ethanol. Other carbon sources include acid and esters such as acetate or formate, or fatty acids having four to twenty-two carbon atoms or fatty acid esters thereof. Other carbon sources can include renewal feedstocks and biomass. Exemplary renewal feedstocks include cellulosic biomass, hemicellulosic biomass and lignin feedstocks. Mixed carbon sources can also be used, such as a fatty acid and a sugar as described herein. In some embodiments, the at least one aldohexose, ketohexose, or aldopentose substrate is selected from the group consisting of glucose, mannose, galactose, fructose, D-xylose, and L-arabinose. In some embodiments only glucose is used as the carbon source. In some embodiments glycerol is used as a sole carbon source or as a combination with glucose. In other embodiments, caffeic acid and / or ferulic acid feeds are combined with the glucose substrate, to enhance titer of tyramine hydroxycinnamic acid amides. Depending on the cell, the appropriate culture medium may be used. For example, descriptions of various culture media may be found in “Manual of Methods for General 4904-4134-6834, v.1 CELB-010-W01 -37- Bacteriology” of the American Society for (Washington D.C., USA, 1981). As used here, “medium” as it relates to the growth source refers to the starting medium be it in a solid or liquid form. “Cultured medium”, on the other hand and as used here refers to medium (e.g. liquid medium) containing microbes that have been fermentatively grown and can include other cellular biomass. The medium generally includes one or more carbon sources, nitrogen sources, inorganic salts, vitamins and / or trace elements. Some aspects of the present disclosure are directed to a cell culture, comprising recombinant host cells as described herein, the cell culture further comprising: a nutrient medium comprising an aldohexose, ketohexose, or aldopentose substrate, wherein the nutrient medium further comprises a buffer, a nitrogen source, amino acids, a pH adjuster, vitamins, minerals, an antibiotic, and / or a cell extract; and tyramine hydroxycinnamic acid amides produced by the recombinant host cells, wherein the tyramine hydroxycinnamic acid amides are present in an amount of at least 1 g / L, at least 1.5 g / L, at least 2 g / L, at least 2.5 g / L, at least 3 g / L, at least 3.5 g / L, at least 4 g / L or more, but less than 50 g / L, 45 g / L, 40 g / L, 35 g / L, or 30 g / L. In some embodiments, the aldohexose substrate is glucose. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 1 g / L, at least 1.5 g / L, at least 2 g / L, at least 2.5 g / L, at least 3 g / L, at least 3.5 g / L, at least 4 g / L, at least 4.5 g / L, at least 5 g / L, at least 5.5 g / L, at least 6 g / L, at least 6.5 g / L, at least 7 g / L or more, but less than 100 g / L, 80 g / L, 75 g / L, 70 g / L, 65 g / L or 60 g / L, wherein the cell culture does not comprise exogenous coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid, and wherein the tyramine hydroxycinnamic acid amides were produced by the recombinant host cells without addition of supplemental coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid. In some embodiments, the nutrient medium further comprises one or more of coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, and ferulic acid. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 10 g / L, at least 11 g / L, at least 12 g / L at least 13 g / L, at least 15 g / L, at least 15.5 g / L, at least 16 g / L, at least 16.5 g / L, 4904-4134-6834, v.1 CELB-010-W01 -38- at least 17 g / L, at least 17.5 g / L, at least 18 least 18.5 g / L, at least 19 g / L, at least 19.5 g / L, at least 20 g / L, at least 20.5 g / L, at least 21 g / L, at least 21.5 g / L, at least 22 g / L, at least 22.5 g / L, at least 23 g / L, at least 23.5 g / L, at least 24 g / L, at least 24.5 g / L, at least 25 g / L, at least 25.5 g / L, at least 26 g / L, at least 26.5 g / L, at least 27 g / L, at least 27.5 g / L, at least 28 g / L, at least 28.5 g / L, at least 29 g / L, at least 29.5 g / L, at least 30 g / L or more, but less than 100 g / L, 75 g / L, or 50 g / L. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise feruloyltyramine in at least 10 g / L, at least 10.5 g / L, at least 11 g / L, at least 11.5 g / L, at least 12 g / L, at least 12.5 g / L, 13 g / L, at least 13.5 g / L, at least 14 g / L, at least 14.5 g / L, at least 15 g / L, at least 15.5 g / L, at least 16 g / L, at least 16.5 g / L, at least 17 g / L, at least 17.5 g / L, at least 18 g / L, at least 18.5 g / L, at least 19 g / L, or more, but less than 100 g / L, 75 g / L or 50 g / L. In some embodiments, the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise caffeoyltyramine in at least 9 g / L, at least 9.5 g / L, at least 10 g / L, at least 10.5 g / L, at least 11 g / L, at least 11.5 g / L, at least 12 g / L, at least 12.5 g / L, at least 13 g / L, at least 13.5 g / L, at least 14 g / L, at least 14.5 g / L, at least 15 g / L, at least 15.5 g / L, at least 16 g / L, at least 16.5 g / L or more, but less than 100 g / L, 75 g / L, or 50 g / L. In some embodiments, the cell culture comprises caffeic acid or ferulic acid, and wherein a portion of the caffeic acid or ferulic acid present is exogenous, not having been produced by the recombinant host cell. In some embodiments, the recombinant host cell comprises nucleic acids which encode a transporter protein that increases uptake of coumaric acid, caffeic acid or ferulic acid, from a culture medium, and wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 10 g / L, at least 10.5 g / L, at least 11 g / L, at least 11.5 g / L, at least 12 g / L, at least 12.5 g / L, at least 13 g / L, at least 13.5 g / L,at least 14 g / L, at least 14.5 g / L, 15 g / L, at least 15.5 g / L, at least 16 g / L, at least 16.5 g / L, at least 17 g / L, at least 17.5 g / L, at least 18 g / L, at least 18.5 g / L, at least 19 g / L, at least 20 g / L, at least 20.5 g / L, at least 21 g / L, at least 21.5 g / L, at least 22 g / L, at least 22.5 g / L, at least 23 g / L, at least 23.5 g / L, at least 24 g / L, at least 24.5 g / L, at least 25 g / L, at least 25.5 g / L, at least 26 g / L, at least 26.5 g / L, at least 27 g / L, at least 27.5 g / L, at least 28 g / L, at least 28.5 g / L, at least 29 g / L, at least 29.5 g / L, at least 30 g / L 4904-4134-6834, v.1 CELB-010-W01 -39- or more, but less than 100 g / L, 75 g / L, or 50 In some embodiments, the tyramine hydroxycinnamic acid amides were produced by the recombinant host cell in a week or less, five days or less, or three days or less. In some embodiments, the tyramine hydroxycinnamic acid amides are produced by the recombinant host cell in five days or less. In some embodiments, the tyramine hydroxycinnamic acid amides are produced by the recombinant host cell in four days or less. In some embodiments, the tyramine hydroxycinnamic acid amides are produced by the recombinant host cell in three days or less. In some embodiments, the tyramine hydroxycinnamic acid amides are produced by the recombinant host cell in two days or less. In some embodiments, the tyramine hydroxycinnamic acid amides are produced by the recombinant host cell in 36 hours or less. The culture conditions can include, for example, liquid culture procedures as well as fermentation and other large-scale culture procedures. Useful yields of the products can be obtained under aerobic culture conditions. An exemplary growth condition for achieving, one or more tyramine hydroxycinnamic acid amide includes aerobic culture or fermentation conditions. In certain embodiments, the microbial organism can be sustained, cultured or fermented under aerobic conditions. Substantially aerobic conditions include, for example, a culture, batch fermentation or continuous fermentation such that the dissolved oxygen concentration in the medium remains between 5% and 100% of saturation. The percent of dissolved oxygen can be maintained by, for example, sparging air, pure oxygen or a mixture of air and oxygen. The culture conditions can be scaled up and grown continuously for manufacturing tyramine hydroxycinnamic acid amides. Exemplary growth procedures include, for example, fed-batch fermentation and batch separation; fed-batch fermentation and continuous separation, or continuous fermentation and continuous separation. All of these processes are well known in the art. Fermentation procedures are particularly useful for the biosynthetic production of commercial quantities of tyramine hydroxycinnamic acid amide products. Generally, and as with non-continuous culture procedures, the continuous and / or near-continuous production of tyramine 4904-4134-6834, v.1 CELB-010-W01 -40- hydroxycinnamic acid amide products will culturing a tyramine hydroxycinnamic acid amide producing organism on sufficient nutrients and medium to sustain and / or nearly sustain growth in an exponential phase. Continuous culture under such conditions can include, for example, 1 day, 2, 3, 4, 5, 6 or 7 days or more. Additionally, continuous culture can include 1 week, 2, 3, 4 or 5 or more weeks and up to several months. Alternatively, the desired microorganism can be cultured for hours, if suitable for a particular application. It is to be understood that the continuous and / or near-continuous culture conditions also can include all time intervals in between these exemplary periods. It is further understood that the time of culturing the microbial organism is for a sufficient period of time to produce a sufficient amount of product for a desired purpose. Fermentation procedures are well known in the art. Briefly, fermentation for the biosynthetic production of tyramine hydroxycinnamic acid amide products can be utilized in, for example, fed-batch fermentation and batch separation; fed-batch fermentation and continuous separation, or continuous fermentation and continuous separation. Examples of batch and continuous fermentation procedures are well known in the art. In some embodiments, the methods further comprise a step of purifying or isolating the tyramine hydroxycinnamic acid amides from the culture. Methods of isolation are not limited and may be any suitable method known in the art. Purification methods include, for example, extraction procedures (e.g., using ethyl acetate, supercritical carbon dioxide, ethanol or mixtures of these two), as well as methods that include continuous liquid-liquid extraction, pervaporation, evaporation, filtration, membrane filtration (including reverse osmosis, nanofiltration, ultrafiltration, and microfiltration), membrane filtration with diafiltration, membrane separation, reverse osmosis, electrodialysis, distillation, extractive distillation, reactive distillation, azeotropic distillation, crystallization and recrystallization, centrifugation, extractive filtration, ion exchange chromatography, size exclusion chromatography, adsorption chromatography, carbon adsorption, hydrogenation, and ultrafiltration or centrifugal partition chromatography (CPC). In some embodiments, the cells are grown in stirred tank fermenters with feed supplementation (sugars with or without organic acids) where the dissolved oxygen, 4904-4134-6834, v.1 CELB-010-W01 -41- temperature, and pH are to be controlled to the optimal growth and production process. In some embodiments, the targeted tyramine hydroxycinnamic acid amide precipitates together with the cell biomass after centrifugation. In one embodiment, an aqueous miscible organic solvent (ethanol, acetonitrile, etc.) is added to the tyramine hydroxycinnamic acid amide containing cell pellet to dissolve the products. Alternatively alkaline water (final pH 12.5-14) is added to the cell pellet to dissolve the hydroxycinnamic tyramines (CT, FT etc). In some embodiments, a simple filtration, ultrafiltration or centrifugation can remove the cells and the aqueous / organic or aqueous alkaline media containing the dissolved products. Ethanol solutions can be evaporated to dryness or to a small volume or ethanol where all tyramine hydroxycinnamic acid amide product remain dissolved and from which they can precipitate or crystalize after addition of 2-4 volumes of water to the remaining ethanol. For the tyramine hydroxycinnamic acid amides dissolved in alkaline water, acidification to a pH of 5.0 to 6.5 causes their precipitation where they can be isolated by filtration. An additional polishing step involving dissolution in Ethanol, removal of insoluble byproducts by filtration, and re- precipitation of tyramine hydroxycinnamic acid amides by the addition of 2-4 volumes of water gives high purity of products. Alternatively, the tyramine hydroxycinnamic acid amide containing cell pellet can be extracted with an aqueous immiscible organic solvent (ethyl acetate, heptane, petroleum ether, etc.) or supercritical carbon dioxide (with 0-10% Ethanol) to extract the tyramine hydroxycinnamic acid amide. Evaporation of the organic solvent and a possible recrystallization will produce pure tyramine hydroxycinnamic acid amide thereof. In some embodiments, an organic solvent is required during growth that is separated at the end of the fermentation. Back extraction with alkaline aqueous solvent or a different organic solvent with low boiling point and high polarity (ethanol, acetonitrile, etc.) will remove the tyramine hydroxycinnamic acid amides. Isolation can then involve a simple pH shift if water is used, or an evaporation if organic solvents are used. In both cases, a recrystallization step may be required at the end to improve purity of the product. 4904-4134-6834, v.1 CELB-010-W01 -42- EXAMPLES Example 1: Selectivity of HCLs for cinnamic (CnA), coumaric (CmA), caffeic (CA), ferulic (FA) acids. HCL activity was observed using the reduced substrate species as a proxy, which is a result of a native reductase that targets the Coenzyme A ligated substrate (CnA-CoA, CmA-CoA, CA-CoA, FA-CoA) (DBR, Figure 3). After transforming plasmids expressing each of HCL1-13 into SB-2697, four separate colonies were patched into 0.5 mL YDCM (yeast nitrogen base + nitrogen, 6.71 g / L; casamino acids, 10 g / L; dextrose monohydrate, 66 g / L; MES hydrate 19.5, g / L; pH adjusted to 6.5 with KOH) with 1 g / L hygromycin in 96dw blocks for 48 h (990 rpm, 30°C) and then diluted back 250x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 24 h (990 rpm, 30°C), 0.5 g / L cinnamic, coumaric, caffeic, or ferulic acid was fed. The cultures were incubated for an additional 8 h or 24 h (990 rpm, 30°C) and then assessed for CnA-R1, CmA-R1, CA-R1, and FA-R1. Table 1: Reduced products (X-R1) made by native DBR when HCLs are expressed and are grown in the presence of Cinnamic (CnA), coumaric (CmA), caffeic (CA) and Ferulic (FA) acids. Products in µM. Strain CnA-R1 CmA-R1 CA-R1 FA-R1 4904-4134-6834, v.1 CELB-010-W01 -43- SB-2697 + 2265 ± 27 ± 77 3752 ± 184 677 ± 73 pCL1219.HCL12 , , , not have activity on cinnamic acid (CnA). Based on this enzyme’s sequence, a number of homologs were cloned (HCL14-18) in plasmid pCL-SE-1219 and were re-screened for activity as described above. Table 2: Reduced products (X-R1) made by native DBR when HCLs are expressed and are grown in the presence of cinnamic (CnA), coumaric (CmA), or caffeic (CA) acids. All are selective for CmA and CA but not CnA, except HCL8 that was used as a control. Products in µM. Strain CnA-R1 CmA-R1 CA-R1 As clearly shown in Table 2, all HCL7 homologs, HCL14-18, do not accept cinnamic acid as a substrate. These enzymes form a distinct class of enzymes sharing 80- 90% sequence identity and low homology to all other HCLs cloned. The only enzyme in this family that has been characterized is HCL7, however, its selectivity was not investigated and was assigned as a feruloyl-CoA synthetase (Sorde, V. et al PLoS ONE, 4904-4134-6834, v.1 CELB-010-W01 -44- 2019, 14(2), e0212629). Structural models and HCL14-18 and investigation of the active site and binding pocket for CmA revealed conserved sequence motifs that may explain the binding of coumaric but not cinnamic acids as shown in Fig 5. These conserved sequence motifs consist of TAXGL (aa 366-370 in HCL7) and IQSDPITSXIK (aa 397-407 in HCL7). Note that X refers to any amino acid. Example 2: Synthesis of caffeoyl-tyramine (CT) from glucose using P450 (CYP98A85) as shown in Figure 2 A plasmid (pCL1219.CmT3H-CYP98A85) expressing CYP98A85 was transformed into strain SB-3080 which expresses TDC7, HCL7, THT1, CYP73, ATR2, and Cytb5 from the genome and thus can convert glucose to CmT. This resulting strain is now able to produce CT from glucose. Four separate colonies of strain SB-3080 / pCL1219.CmT3H-CYP98A85 were patched into 0.5 mL YDCM with 1 g / L hygromycin in 96dw blocks for 48 h (990 rpm, 30°C) and then assessed for CmA, CmT, and CT. Table 3: Production of coumaric acid (CmA), coumaroyl-tyramine (CmT), and caffeoyl- tyramine (CT) from glucose in an engineered CmT-producing Y. lipolytica strain that expresses CYP98A85. Products in µM. Strain CmA CmT CT The above example clearly shows that CYP98A85 converts CmT to CT. However, in this example, residual CmT remained in the media, suggesting that the activity of the hydroxylase needs to be improved to convert all CmT to the final CT product. To improve CYP98A85 activity, various approaches will be taken, as described in the specifications. 4904-4134-6834, v.1 CELB-010-W01 -45- Example 3: Selectivity and activity of caffeic acid and CT. OMT activity was determined by monitoring the production of ferulic or isoferulic acid and FT or Iso-FT from caffeic acid and CT, respectively. After transforming plasmids expressing OMT1-10 into SB-2697, four separate colonies were patched into 0.5 mL YDCM with 1 g / L hygromycin in 96dw blocks for 48 h (990 rpm, 30°C) and then diluted back 250x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 24 h (990 rpm, 30°C), 0.5 g / L caffeic acid or 1.5 mM CT was fed. The cultures were incubated an additional 48 h (990 rpm, 30°C) and then assessed for FA, Iso-FA, FT, and Iso-FT. Table 4: Methylation products after feeding caffeic acid and caffeoyl tyramine in cells expressing OMTs. Products in µM. Strain Caffeic acid (CA) feed Caffeoyl-tyramine (CT) feed 4904-4134-6834, v.1 CELB-010-W01 -46- The results in Table 4 show that many OMTs can methylate CT to produce FT, OMT9 was the most active for this transformation. Incorporation of this enzyme in a CT producing strain results in production of FT (Example 4). Also it is also clear in this example that OMT1 methylates caffeoyl tyramine to iso-FT. Example 4: Selectivity and activity of AMLs on L-phenylalanine or L-tyrosine. AML activity was determined by monitoring the production of cinnamic or coumaric acid. After transforming plasmids expressing AML2-10 into SB-2130, four separate colonies were patched into 0.5 mL YDCM with 1 g / L hygromycin in 96dw blocks for 48 h (990 rpm, 30°C) and then diluted back 250x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 48 h (990 rpm, 30°C), the cultures were assessed for CnA and CmA. Table 5: Production of cinnamic or coumaric acid from phenylalaine or tyrosine, respectively, In Y lipolytica strains expression AMLs. Products in µM. Strain CnA CmA 4904-4134-6834, v.1 CELB-010-W01 -47- These data show that various AMLs with no activity on phenylalanine were discovered. Example 5: Selectivity and activity of tyrosine decarboxylases (TDCs) on L- phenylalanine or L-tyrosine. In all pathways described herein enzyme selectivity of certain key steps is important to reduce byproducts. One such step is the decarboxylation of tyrosine to tyramine by decarboxylases (TDCs) that do not also decarboxylate phenylalanine to phenylethylamine (PhM). Once PhM is formed, it is quickly incorporated into final products (similar to tyramine) to produce coumaroyl-PhM, caffoyl-PhM and feruloyl- PhM. Identifying TDCs with minimal or no activity for phenylalanine decarboxylation was achieved after screening of various TDC as shown in Table 6. TDC activity was determined by monitoring the production of phenylethylamine or tyramine from L-phenylalanine or L-tyrosine, respectively. After transforming plasmids expressing TDC1-9 into SB-2130, six separate colonies were patched 0.5 mL YDCM with 1 g / L hygromycin 96dw blocks for 48 h (990 rpm, 30°C) and then diluted back 250x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 48 h (990 rpm, 30°C), the cultures were assessed for phenylethylamine and tyramine. Table 6: Decarboxylation products of phenylalanine (to PhM) and tyrosine (to TyM) in Y. lipolytica cells expressing different TDCs and grown on glucose. Products in µM. Strain Phenylethylamine Tyramine (TyM) TyM / PhM 4904-4134-6834, v.1 CELB-010-W01 -48- SB-2130 + pCL1219.TDC5 508 ± 16 7825 ± 278 15.5 p g . p y without any modifications of the aromatic amino acid pathway and thus show the selectivity of each enzyme in a strain that naturally produces both Phe and Tyr. Clearly, TDC7 is the most selective TDC for tyrosine over phenylalanine, while TDC8 and TDC9 show higher activity but produce small amounts PhM. Example 6: Selectivity and activity of THTs on coumaric, caffeic, and ferulic acid. THT activity was determined by monitoring the production of coumaroyl- tyramine (CmT), caffeoyl-tyramine (CT), and feruloyl-tyramine (FT) from coumaric, caffeic, and ferulic acids, respectively, with the co-expression of HCL2 or HCL8. Tyramine is produced by the cells from glucose via the amino acid biosynthesis pathway and TDC7. After transforming plasmids expressing THT1,3,19,20,22,24-27,31,32 and HCL2 or HCL8 into SB-2723, four separate colonies were patched into 0.5 mL YDCM with 1 g / L hygromycin in 96dw blocks and precultured for 48 h (990 rpm, 30 °C) and then diluted back 250x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 24 h (990 rpm, 30°C), 0.5 g / L coumaric, caffeic, or ferulic acid was fed. The cultures were incubated for an additional 24 h (990 rpm, 30°C) and then assessed for CmT, CmT-R1, CT, CT-R1, FT, and FT-R1. Because DBR was present in the strain, tyramine amides and amides made from reduced cinnamic acids are reported (Figure 3). 4904-4134-6834, v.1 CELB-010-W01 -49- Table 7: THT screening with coumaric, or ferulic acid feed in the presence of HCL2. Products in µM. Strain Coumaric feed Caffeic feed Ferulic feed Table 8: THT screening with coumaric, caffeic, or ferulic acid feed in the presence of HCL8. Products in µM. Strain Coumaric feed Caffeic feed Ferulic feed 4904-4134-6834, v.1 CELB-010-W01 -50- SB-2723 + pCL1219.THT19 1738 ± 171 1574 ± 113 2093 ± 197 The above results showed that all active THTs can utilize all cinnamoyl-CoA substrates, however, they do show different preferences. Example 7: Elimination of iso- methylated products: knockout of OMT1 It was observed that wild type Y. lipolytica methylates caffeic acid to iso-ferulic acid (Figure 3). The genome of Y. lipolytica contains one gene, YALI0_B03124g or OMT1 herein, that is annotated as a putative o-methyltransferase. This gene was disrupted to examine its effect on Y. lipolytica's ability to convert caffeic acid to isoferulic acid. This strain and the parent were tested for the resulting strain’s ability to convert caffeic acid to 4-methoxy-caffeic acid in 96-well fermentations. Fermentations were carried out as follows. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 250x into 0.5 mL fresh YDCM. After 24 h (990 rpm, 30°C), 0.5 g / L caffeic acid was fed. The cultures were incubated for an additional 48 h (990 rpm, 30°C) and then assessed for CA and Iso-FA. As shown in 4904-4134-6834, v.1 CELB-010-W01 -51- Table 9, production of isoferulic acid by Y. was eliminated by disruption of OMT1. Table 9: Disruption of OMT1 eliminates conversion of CA to Iso-FA. OMT1 intact strain, SB-2130, and ∆OMT1 strain, SB-2626, were grown in YDCM for 24 h then fed 0.5 g / L (2.8 mM) CA. Cultures were incubated for an additional 24 h and analyzed for CA and Iso-FA. Products in mM. Strain CA Iso-FA Example 8: Reduction of reduced cinnamic, coumaric, caffeic, and ferulic acid by- products: knockout of DBR As described earlier, in the presence of HCL, Y. lipolytica strains can reduce cinnamic acids to their corresponding dihydro analogs, as shown in Figure 3 (CA-R1, FA-R1, and CmA-R1). This activity was also reported in Saccharomyces cerevisiae and the responsible enzyme was identified as a side reaction of an enoyl-CoA reductase, TSC13 (Lehka, BJ, et al FEMS Yeast Research, 17(1), fox004). A similar enzyme was identified in Y. lipolytica: Uniprot Q6CHU1, which we will refer to as YlTSC13. Similar to TSC13 in S. cerevisiae, YlTSC13 could not be disrupted (data not shown) and hence is likely also essential in Y. lipolytica. Thus, we tested the role of TSC13 by replacing it with either the enoyl-CoA reductase from Arabidopsis thaliana (AtECR) or Malus domestica (MdECR). SB-2689 carries HCL1 and THT1 and when fed cinnamic, coumaric, caffeic, or ferulic acid, the respective reduced products are formed. It is worth noting that OMT1 is intact in this strain and thus the caffeic acid is also converted to isoferulic acid which is 4904-4134-6834, v.1 CELB-010-W01 -52- reduced to its dihydro- derivative. this strain is also fed tyramine, it produced tyramine conjugated derivatives from all feeds as well as their reduced derivatives. The YlTSC13 gene in strain SB2689 was replaced with genes expressing AtECR (Q9M2U2) or MdECR (XP_008382818) to generate strains SB-2734 and SB- 2735, respectively. Seed cultures of these strains were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 24 h (990 rpm, 30°C), 0.5 g / L tyramine and 0.5 g / L cinnamic, coumaric, caffeic, or ferulic acid was fed. The cultures were incubated for an additional 24 h (990 rpm, 30°C) and then assessed. Tables 10a-d show the results of these assays. In all cases, the strains with YlTSC13 replaced with either AtECR or MdECR have significant reduction in the various reduced species (-R1) compared to the parent strain, SB-2689. Table 10a: Product formation from cinnamic acid (CnA) feeds in strains with native YlTSC13 (SB-2689) and YlTSC13 replaced with AtECR (SB-2734) or MdERC (SB- 2735) insertion. Products in µM. Strain CnA CnA- CnT CnT- R1 R1 Table 10b: Product formation from coumaric acid (CmA) feeds in strains with native YlTSC13 (SB-2689) and YlTSC13 replaced with AtECR (SB-2734) or MdERC (SB- 2735) insertion. Products in µM. Strain CmA CmA- CmT CmT- 4904-4134-6834, v.1 CELB-010-W01 -53- SB-2734 1630 258 239 0 (CA) feeds in strains with native YlTSC13 (SB-2689) and YlTSC13 replaced with AtECR (SB-2734) or MdERC (SB- 2735) insertion. Products in µM. Strain CA CA- CT CT Iso- Iso-FA- Iso- FT Iso-FT- FT- R1 -R1 FA R1 FT R1 R1 Table 10d: Product formation from ferulic acid (FA) feeds in strains with native YlTSC13 (SB-2689) and YlTSC13 replaced with AtECR (SB-2734) or MdERC (SB- 2735) insertion. Products in µM. Strain FA FA-R1 FT FT- R1 The results from caffeic acid feed (Table 10c) were complicated due to the production of isoferulic acid by OMT1, so similar experiments were done in strains with OMT1 disrupted (SB-2972). Again, YlTSC13 was disrupted and replaced with genes expressing either AtECR or MdECR to generate strains SB-3040 and SB-3046. Fermentations were carried out as before and Table 10e shows the results. Again, the 4904-4134-6834, v.1 CELB-010-W01 -54- strains with YlTSC13 replaced with either or MdECR have significant reduction in the various reduced species (-R1) compared to the parent strain, SB-2972. Table 10e: Product formation from caffeic acid (CA) feeds in strains with native YlTSC13 (SB-2972) and YlTSC13 replaced with AtECR (SB-3040) or MdERC (SB- 3046) insertion. Products in µM. Strain CA CA- CT CT- R1 R1 The above results clearly show that YlTSC13 is responsible for reducing all hydroxy-cinnamoyl-CoAs as shown in Figure 3. In addition, expression of AtECR and MdECR restored viability to YlTSC13 inactivated strains without reducing the hydroxy- cinnamoyl-CoAs. Example 9: Elimination of oxidized tyramine products: knockout of MAO3 Y. lipolytica strains that produce tyramine were observed to produce hydroxy- phenyl-acetic acid (HPAA) and hydroxy-phenyl-ethanol (HPE). These compounds are both derived from hydroxy-phenyl-acetaldehyde (HPAL), which in turn is derived from tyramine (Figure 4). The enzyme that produces HPAL from tyramine is a mono-amine oxidase. Y. lipolytica has three genes that encode for mono-amine oxidase, MAO1 (Q6CGT2; YALI0_A16445g), MAO2 (Q6CB09; YALI0_C22792g), and MAO3 (Q6CBJ1; YALI0_C18315g). We argued that both HPAA and HPE could be reduced or eliminated by disruption one or more of these MAO genes. Thus, each of these genes were disrupted in a strain that produces tyramine and expresses a tyrosine decarboxylase 4904-4134-6834, v.1 CELB-010-W01 -55- (SB-2691). The effects of these disruptions assessed in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 48 h (990 rpm, 30°C), these cultures were assessed for tyramine and tyramine-derived products. As can be seen in Table 11, both HPAA and HPE are eliminated with the disruption of MAO3. Table 11: Tyramine and derivatives formed in strains with native MAOs (SB-2691) and strains with MAO1 (SB-2842), MAO2 (SB-2843), or MAO3 (SB-2844) inactivated. Products in µM. Strain Gene Tyramin HPE HPAA Acetyl-tyramine disrupted e Example 10: Reduction of acetyltyramine All Y. lipolytica strains that produce tyramine also produce acetyltyramine as a byproduct (Figure 4). We hypothesized that this is likely a side-reaction of an acetyltransferase that transfers an acetyl group to a terminal amine. Such enzymes are: ECO1 (N-acetyltransferase O1 (establishment of cohesion protein 1), YALI0_E12023g), ESA1 (histone acetyltransferase,YALI0_E04675g), GCN5 (histone acetyltransferase, YALI0_E02772g), LYC1 (lysine acetyltransferase (lysine N(6)-acetyltransferase), YALI0_E05533g), HAT1 (histone acetyltransferase 1, YALI0_C11231g), and PAA1 (polyamine acetyltransferase homolog, YALI0_B14036g). Each of these genes were disrupted in a strain that produces tyramine and carries a tyrosine decarboxylase (SB- 4904-4134-6834, v.1 CELB-010-W01 -56- 2723). Of these genes, we found that HAT1 or GCN5 resulted in a significant reduction in acetyl-tyramine (Table 12). Consistent with the reduction in acetyl-tyramine, increases in the other tyramine by-products, HPE and HPAA, were observed. Table 12: Tyramine and derivatives formed in a strain with native acetyltransferases (SB- 2723) and strains with ECO1 (SB-2936), ESA1 (SB-2938), GCN5 (SB-2940), LYC1 (SB- 2942), HAT1 (SB-2944), or PAA1 (SB-2946) inactivated. Products in µM. Strain Gene Tyramine HPE HPAA Acetyl-tyramine disrupted Additionally, we argued that reducing the intracellular levels of acetyl-CoA could also reduce this unwanted side-reaction. To examine this idea, ATP-citrate lyase (ACL1) was disrupted in the tyramine producing strain, SB-2723 and resulted in reduced levels of acetyltyramine (Table 13). Table 13: Tyramine and derivatives formed in a strain with native acetyltransferases (SB- 2723) and a strain with ACL1 (SB-2934) inactivated. Products in µM. Strain Gene Tyramine HPE HPAA Acetyl-tyramine 4904-4134-6834, v.1 CELB-010-W01 -57- SB-2723 -- 1157 143 569 , , eduction of acetyl-tyramine. Combining disruptions of ACL1, HAT1, and GCN5 may further reduce acetyl-tyramine levels. Example 11: Increasing uptake of caffeic and ferulic acids: expression of HBTs To examine if uptake of caffeic acid could be improved, two hydroxy-benzoic acid transporters (HBT1 and HBT2) from Candida parapsilosis were overexpressed in WT Y. lipolytica (SB-2130). WT Y. lipolytica is able to efficiently convert caffeic acid to isoferulic acid, thus production of isoferulic acid was used as a read-out for caffeic acid uptake. These strains were assayed in caffeic acid-feed fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 24 h (990 rpm, 30°C), 0.5 g / L CA was fed. The cultures were incubated for an additional 12 h (990 rpm, 30°C) and then assessed for CA and iFA. As can be seen in Table 14, production of isoferulic acid is significantly increased in strains expressing HBT1 and HBT2. Thus, HBT1 and HBT2 improve uptake of CA into Y. lipolytica cells. Table 14: Isoferulic acid (iFA) formed from CA in WT Y. lipolytica (SB-2130) and WT Y. lipolytica overexpressing HBT1 or HBT2. Products in µM. Strain Gene CA iFA 4 4904-4134-6834, v.1 CELB-010-W01 -58- BLAST searches against the Y. lipolytica genome using HBT1 and HBT2 as seeds identified a transporter (YALI0_E21241g) with high sequence identity to both. To examine if this transporter, which we call YlMFP2, is able to increase uptake of caffeic acid, we overexpressed it in a Y. lipolytica strain (SB-2971) carrying HCL1, THT1, and TDC7. Furthermore, this strain has a disruption of OMT1. Increased uptake is expected to result in reduced free CA remaining and increased CA-derived products (CA-R1, CT, CT-R1). These strains were assayed in caffeic acid-feed fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 24 h at (990 rpm, 30°C), 0.5 g / L CA was fed. The cultures were incubated for an additional 24 h (990 rpm, 30°C) and then assessed for CA, CA-R1, CT, and CT-R1. As is evident in Table 15, overexpression of the Y. lipolytica transporter results in reduced free CA remaining and increased CA-derived products. Thus, YlMFP2 is able to improve uptake of CA into Y. lipolytica cells. Table 15: CA-derived products formed from CA in a strain with native YlMFP2 expression (SB-2971) and a strain overexpressing YlMFP2 (SB-2971 + pCL-2034). Products in µM. Strain Gene overexpressed CA CA-R1 CT CT-R1 To examine if these or other transporters can improve FA uptake, a strain is being built with TDC7 and multiple copies of HCL and THT. These enzymes are needed to observe conversion of FA to products and multiple copies of HCL and THT are needed to ensure that conversion of FA to product is not limiting. HBT1, HBT2, and the YlMFP2 will be introduced into the strain and examined for increased rate of conversion of FA to products. 4904-4134-6834, v.1 CELB-010-W01 -59- Example 12: Increasing aromatic amino acid flux: expression of ARO4 We have found that overexpression of ARO4 (3-deoxy-D-arabino-heptulosonate- 7-phosphate synthase) was effective in increasing metabolic flux to phenylalanine and tyrosine. ARO4 is the first enzyme in the chorismate metabolism pathway that leads to aromatic amino acids tryptophan, tyrosine, and phenylalanine. To examine the effect of ARO4 overexpression on phenylalanine and tyrosine production, an ARO4 overexpression cassette was integrated at the MAO3 locus in SB- 3080, a strain carrying the enzymes to convert phenylalanine to cinnamic acid (PAL), cinnamic to coumaric acid (AtC4H (CYP73A5), AtATR2, and ScCYB5), tyrosine to tyramine (TDC7), and coumaric acid plus tyramine to CmT (HCL7 and THT1). These strains were examined in 96-well fermentation. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 48 h (990 rpm, 30°C), the cultures were assessed for phenylalanine and tyrosine derivatives. As can be seen Table 16, overexpression of ARO4 resulted in a significant increase in the production of phenylalanine-derived products (CnA, CnA-R1, CmA, CmA-R1, CmT, and CmT-R1; Table16a) and tyrosine-derived products and by- products (TyM, CmT, CmT-R1, HPE, HPAA, and Ace-TyM; Table16b), indicating the increased flux to phenylalanine and tyrosine, respectively. Table 16a: Phenylalanine-derived products formed in a strain with native ARO4 expression (SB-3080) and a strain overexpressing ARO4 (SB-3165). Products in µM. Strain Gene CnA CnA- CmA CmA- CmT CmT- Total 6 9 4904-4134-6834, v.1 CELB-010-W01 -60- Table 16b: Tyrosine-derived products a strain with native ARO4 expression (SB-3080) and a strain overexpressing ARO4 (SB-3165). Products are in µM. Strain Gene TyM CmT CmT- HPE HPAA Ace- Total overexpressed R1 Tym 3 97 y p , p p p dehydrogenase; EC 1.3.1.13), which is responsible for the first specific step in tyrosine production. TYR1 was overexpressed in SB-2873, a strain that produces coumaric acid from phenylalanine via cinnamic acid (PAL, AtC4H, AtATR2, and ScCYB5) and tyramine from tyrosine (TDC7). The resulting strain, SB-3137, and the parent strain, SB- 2873, were assessed in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM with 1 g / L hygromycin in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM with 1 g / L hygromycin. After 48 h, the cultures were assessed for phenylalanine and tyrosine derivatives. As is evident in Table 17, overexpression of TYR1 resulted in a significant increase in tyrosine-derived tyramine products (TyM, HPE, HPAA, and Ace-TyM) while the phenylalanine-derived cinnamic and coumaric acids were reduced. This result indicates that TYR1 overexpression increases flux to tyrosine while reducing flux to phenylalanine. Table 17: Phenylalanine- and tyrosine- derived products formed in strain with native ARO4 expression (SB-2873) and strain overexpressing ARO4 (SB-3137). Products are in µM. Phe Tyr products 4904-4134-6834, v.1 CELB-010-W01 -61- SB- -- 6512 218 727 994 8451 2873 , , PHA2 (Prephenate dehydrogenase; EC 4.2.51), which is responsible for the first specific step in phenylalanine production. PHA2 will be overexpressed in SB-2783, a strain that produces coumaric acid from phenylalanine and tyramine from tyrosine. Example 13: Formation of FT by ferulic acid-feed To produce FT from feeding ferulic acid, HCL (HCL1, HCL7, HLC8, and HCL11) and THT (THT1 and THT19) combinations were introduced into SB-3290, a strain with MAO3 disrupted (eliminates HPE and HPAA), TSC13 disrupted, MdECR expressed (decreases reduced products), TDC7 expressed (produces tyramine), ARO4 overexpressed (increases flux to tyrosine), and HBT1 expressed (improves uptake of hydroxy-cinnamoic acids). These strains were assessed in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 24 h (990 rpm, 30°C), the cultures were fed 0.5 g / L ferulic acid. After an additional 8 h (990 rpm, 30°C), the cultures were assessed for ferulic acid and FT. Results are shown in Table 18. As can be seen, all combinations of HCL and THT resulted in FT production. Table 18: FT formed from FA in strains expressing various HCLs (HCL1, HCL7, HLC8 & HCL11) and THTs (THT1 and THT19). Products in µM. Strain HCL THT FA FT 4904-4134-6834, v.1 CELB-010-W01 -62- SB-3375 HCL7 THT1 1781 Example 14: Formation of CT from caffeic acid-feed To produce CT from feeding caffeic acid, HCL (HCL1, HCL7, HCL9, and HCL12) and THT (THT1, THT19, THT26, and THT27) combinations were introduced into SB-3347, a strain with OMT1 disrupted (eliminates isoferulic acid), MAO3 disrupted (eliminates HPE and HPAA), TSC13 disrupted, MdECR expressed (decreases reduced products), TDC7 expressed (produces tyramine), ARO4 overexpressed (increases flux to tyrosine), and HBT1 expressed (improves uptake of hydroxy-cinnamoic acids). These strains were assessed in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 24 h (990 rpm, 30°C), the cultures were fed 1 g / L caffeic acid. After an additional 6 h (990 rpm, 30°C), the cultures were assessed for caffeic acid and CT. Results are shown in Table 19. As can be seen, all combinations of HCL and THT resulted in CT production. Table 19: CT formed from CA in strains expressing various HCLs (HCL1, HCL7, HLC9 & HCL11) and THTs (THT1, THT19, THT26 & THT27). Products in µM. 4904-4134-6834, v.1 CELB-010-W01 -63- Strain HCL THT CA CT Example 15: Formation of CmT from glucose (SB-3021) To examine if CmT could be produced from glucose, genes expressing HCL7, THT1, and MdECR were introduced into the YlTSC13 locus of SB-2873, a strain that produces CmA from phenylalanine and tyramine from tyrosine, to generate SB-3021. 4904-4134-6834, v.1 CELB-010-W01 -64- These strains were examined in 96-well Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM001. After 48 h (990 rpm, 30°C), the cultures were assessed for CmT production (Table 20). As is evident, SB-3021 was able to produce CmT from glucose. Table 20: CmT formed from glucose when HCL7 and THT1 are introduced (SB-3021) into a strain engineered to produce CmA from phenylalanine and TyM from tyrosine (SB-2873). Products in µM. Strain CmA CmT Example 16: Formation of CT from glucose (SB-3222) To examine if CT could be produced from glucose, CYP98A85 (converts CmT to CT) was introduced into the CmT producing strain SB-3080 to generate SB-3222. SB- 3080 carries the enzymes to convert phenylalanine to cinnamic acid (PAL), cinnamic to coumaric acid (AtC4H (CYP73A5), AtATR2, and ScCYB5), tyrosine to tyramine (TDC7), and coumaric acid plus tyramine to CmT (HCL7 and THT1). These strains were examined in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 48 h (990 rpm, 30°C), the cultures were assessed for CT production (Table 21). As is evident, SB-3222 was able to produce CT from glucose. Table 21: CT formed from glucose when CYP98A85 is introduced (SB-3222) into a strain engineered to produce CmT from phenylalanine-derived CmA and tyrosine- derived TyM (SB-3080). Products in µM. 4904-4134-6834, v.1 CELB-010-W01 -65- Strain CmA CmT CT cose (SB-3339) To examine if FT could be produced from glucose, genes expressing CYP98A85 (converts CmT to CT) and OMT9 (converts CT to FT) were introduced into the CmT producing strain, SB-3080, to generate SB-3339. SB-3080 carries the enzymes to convert phenylalanine to cinnamic acid (PAL), cinnamic to coumaric acid (AtC4H (CYP73A5), AtATR2, and ScCYB5), tyrosine to tyramine (TDC7), and coumaric acid plus tyramine to CmT (HCL7 and THT1). These strains were examined in 96-well fermentations. Seed cultures were grown in 0.5 mL YDCM in 96dw blocks for 24 h (990 rpm, 30°C) and then diluted back 50x into 0.5 mL fresh YDCM. After 48 h (990 rpm, 30°C), the cultures were assessed for FT production (Table 22). As is evident, SB-3339 was able to produce FT from glucose. Table 22: FT formed from glucose when CYP98A85 and OMT9 is introduced (SB-3339) into a strain engineered to produce CmT from phenylalanine-derived CmA and tyrosine- derived TyM (SB-3080). Products in µM. Strain CmA CmT CT FT 4904-4134-6834, v.1 CELB-010-W01 -66- Example 18: Increased formation of CT and from glucose using improved CYP98A85 (CmT3H) To increase the flux to and titers of CT and FT from glucose, the enzyme that converts CmT to CT, CYP98A85, must be improved. Exact methods for the improvement of this enzyme are described in the specifications and involve mutagenesis of 1 to 48 amino acids and / or co-expression with native P450 reductases (CPRs) and / or fusions of CYP98A85 with CPRs. All mutants and combinations will be tested for increased CT production in SB-3080 (PAL, AtC4H, AtATR2, ScCYB5, TDC7, HCL7, and THT1), as described in Example 16, or another strain that produces CmT from glucose (Figure 2). Example 19: High titer fermentation of FT and CT using caffeic / ferulic acid feeds Production of high titers of FT and CT were achieved in 2 L fermenters. A typical process for the manufacturing of CT and FT with caffeic acid (CA) and ferulic acid (FA) supplementation is described. In one 250 mL baffled flask containing 50 mL of PM001 media (10 g / L yeast extract, 20 g / L peptone, 20 g / L dextrose), one colony of strain SB3403 is inoculated. After 24 h of growth at 30 °C with shaking, 20 mL of this culture is added to a 1 L fermenter containing PM002 media (3.4 g / L yeast nitrogen base without ammonium sulfate, 20 g / L casamino acids, 10 g / L ammonium sulfate and 100 g / L dextrose, pH 6.0). The fermentation settings consist of 30 °C temperature, 20% dissolved oxygen (DO) and 0.7 vvm of airflow. The foaming is controlled by additions of J-673 antifoam as needed. The cells are allowed to grow, and the DO is controlled at 20% by agitation throughout the fermentation run. Glucose is always in excess and is maintained between 5-50 g / L throughout the fermentation. After 18 h of inoculation with cells, and an OD600 of >60, each of CA or FA are added as concentrated solutions (dissolved in alkaline water) in the fermenter over ~10 min while the pH is adjusted to 6 immediately after the addition. The later CA and FA stock solutions were prepared by dissolving 13 g of caffeic or ferulic acid in 25 mL of 5 N KOH. After the addition the fermentation 4904-4134-6834, v.1 CELB-010-W01 -67- continues until a total of 72 h (by 20%, and excess glucose). At this point ~12-15 g / L of CT and ~15-18 g / L of FT have been produced, while the final volume in the fermenter is ~1.1-1.2 L. None of the other major byproducts were produced from the action of OMT1, MAO3, and TSC13 as shown in Figure 3 and hydroxyphenyl acetic acid (HPAA) and hydroxyphenyl ethanol (HPE) shown in Figure 4. In addition, no acetyl tyramine was observed due to the presence of caffeic or ferulic acid throughout the fermentation run (final concentration of CA or FA ~0.5-1 g / L) Example 20: High titer fermentation of CT and FT using glucose-only feed Production of CT and FT from glucose was also achieved in the fermenter. Strain SB3236 that contains all enzymes required for the synthesis of coumaroyl-tyramine from glucose as well as the two enzymes that convert it to CT and FT was used for the production of FT from glucose (as shown in Figure 2). The cells were grown in a 2 L fermenter as described in Example 19, with the only difference being that no caffeic or ferulic acids were added in the media and the fermentation was extended to 5 days (120 h). Under these conditions, SB3236 produced: 4 g / L of FT, 0.06 g / L of CT, 1.4 g / L CmT, 3 g / L CmA, and 0.8 g / L of TyM. Example 21: Purification of CT and FT from fermentation broth A downstream process protocol that isolates CT and FT from fermentation broth in high yield and purity was developed. Specifically, for 1 L of CT or FT containing fermentation the following purification steps are applied: Step-1: fermentation broth (1 L, pH 5.5-6) is centrifuged to precipitate cells along with CT or FT Step-2: The cell pellet with CT or FT is resuspended in 0.15 M NaOH solution (1 -1.2 L) where after mixing the pH is measured to be >12.5. After good mixing for 10 min the broth is centrifuged to remove the cells. The alkaline filtrate is collected and the pH is 4904-4134-6834, v.1 CELB-010-W01 -68- adjusted by the addition of mineral acid (14 or hydrochloric) between 5.5- 6.5 to precipitate CT and FT in a flask with good stirring over a period of 30-60 minutes. The precipitate is isolated by filtration. Step-3: the precipitate from the above step is mixed with ethanol (22 mL EtOH per gram CT and 5 mL EtOH per gram of FT). After good mixing for 10 min the solution is filtered to remove insoluble impurities and the clarified ethanol filtrate is mixed with 4 volumes of water. This solution is stirred for a period of 5-30min resulting in a precipitate of CT and FT that is removed by filtration. The overall purification produces >80% overall yield and >95% purities for both CT and FT Table 23: purification steps and results of CT and FT fermentation broths Step Description CT broth 13.7 g / L FT broth 14.5 / L Example 22: Elimination of acetyl-tyramine from fermentation by excess caffeic / ferulic feed It was observed that excess of caffeic or ferulic acid in the fermentation broth significantly reduces the amount of acetyl-tyramine (Ace-TyM). Strain SB3972 was grown as described in Example 19. The only difference was that the addition of FA was performed in two doses, one at 20 h (2 g / L) and at 28 h (1.5 g / L). Table 24: effect of the concentration of ferulic acid accumulation and acetyl-tyramine. 4904-4134-6834, v.1 CELB-010-W01 -69- Time (hrs) FA (µM) FT (µM) TyM (µM) AceTyM (µM) 0 4 5 1 8 3 1 2 0 The results of Table 24 clearly show that when FA concentration was below 100 µM acetyl-tyramine (Ace-TyM) started accumulating at high rates. Under these conditions tyramine (TyM) was converted to acetyl-tyramine strongly suggesting that if caffeic or ferulic are not available to remove TyM as CT and FT, the accumulated tyramine is converted to Ace-TyM byproduct. Table 25: list of strains Strain Genes overexpressed Gene disruptions 4904-4134-6834, v.1 CELB-010-W01 -70- SB-2723 TDC7 ∆omt1 4904-4134-6834, v.1 CELB-010-W01 -71- SB-3236 C4H, AtATR2, Cytb5, MdECR, ∆omt1, ∆mao3, ∆yltsc13 THT1, HCL7, ARO4, OMT9, CmT3H 4904-4134-6834, v.1 CELB-010-W01 -72- SB-3496 TDC7, HBT1, MdECR, THT26 ∆mao3, ∆yltsc13, ∆omt1 Table 24: Enzymes expressed and tested Enzyme Name EC Uniprot or NCBI 4904-4134-6834, v.1 CELB-010-W01 -73- HCL17 CoA 6.2.1.12 A0A1M3HN83 ligase 4904-4134-6834, v.1 CELB-010-W01 -74- TDC8 Tyrosine decarboxylase 4.1.1.25 A0A077RVL1 4904-4134-6834, v.1 CELB-010-W01 -75- OMT8 O-methyltransferase 2.1.1.42 / 68 A7U0E5 Table 25: Key enzymes inactivated in Y. lipolytica Enzyme Name EC Uniprot or NCBI 4904-4134-6834, v.1 CELB-010-W01 -76- OMT1 O4’-methyltransferase 2.1.1.- Q6CFW1 4904-4134-6834, v.1 CELB-010-W01 -77- LISTING OF AMINO ACID SEQUENCES >TDC001 (SEQ ID NO: 1) MKNEKLAKGEMNLNALFIGDKAENGQLYKDLLIDLVDEHLGWRQNYMPQDMP VISSQERTSESYEKTVNHMKDVLNEISSRMRTHSVPWHTAGRYWGHMNSETLMP SLLAYNFAMLWNGNNVAYESSPATSQMEEEVGHEFAHLMSYKNGWGHIVADGSL ANLEGLWYARNIKSLPFAMKEVKPELVAGKSDWELLNMPTKEIMDLLESAEDEID EIKAHSARSGKHLQAIGKWLVPQTKHYSWLKAADIIGIGLDQVIPVPVDHNYRM DINELEKIVRGLAEEQIPVLGVVGVVGSTEEGAVDSIDKIIALRDELMKDGIYYYV HVDAAYGGYGRAIFLDEDNNFIPYEDLQDVHEEYGVFKEKKEHISREVYDAYKA IELAESVTIDPHKMGYIPYSAGGIVIQDIRMRDVISYFATYVFEKGADIPALLGAYIL EGSKAGATAASVWAAHHVLPLNVAGYGKLIGASIEGSHHFYNFLNDLTFKVGDK EIEVHTLTHPDFNMVDYVFKEKGNDDLVAMNKLNHDVYDYASYVKGNIYNNEFI TSHTDFAIPDYGNSPLKFVNSLGFSDEEWNRAGKVTVLRAAVMTPYMNDKEEFD VYAPKIQAALQEKLEQIYDVK >TDC005 (SEQ ID NO: 2) MSESLSKDLNLNALFIGDKAENGQIYKALLNELVDEHLGWRQNYMPQDMPIITP EEKSSASFEHTVNKTKDVLSEISARMRTHSVPWHNAGRYWGHMNSETLMPSLLA YNFAMLWNGNNVAYESSPATSQMEEEVGMEFAKLMSYKDGWGHIVADGSLANL EGLWYARNIKSLPLAMKEVTPELVAGKSDWELMNLSTEEIMNLLDSVPEKIDEIK AHSARSGKHLEKLGKWLVPQTKHYSWLKAADIIGIGLDQVIPVPVDHNYRMDIN ELEKIVRGLAAEKTPILGVVGVVGSTEEGAIDGIDKIVALRRVLEKDGIYFYLHVD AAYGGYGRAIFLDEDNNFIPFEDLKDVHYKYNVFTENKDYILEEVHSAYKAIEEA ESVTIDPHKMGYVPYSAGGIVIKDIRMRDVISYFATYVFEKGADIPALLGAYILEGS KAGATAASVWAAHHVLPLNVTGYGKLMGASIEGAHRFYNFLNDLSFKVGDKEIE VHPLTYPDFNMVDYVFKEKGNDDLVAMNKLNHDVYDYSSYVKGSIYGNEFLTS HTDFAIPDYGNSPLQFVNQLGFSDEEWNRAGKVTVLRASVMTPYMNKEEHFEEY AEKIKAALQEKLEKIYADQLLASEAK >TDC007 (SEQ ID NO: 3) MAPPSHFSNVAATVPVVVDKPQQCSNALDADDFRRQGHQVIDFIAEYYGGMAD YPVHPSVTPGFLRNLLPASAPSRAEPDAFSSALKDIRDHILPGMTHWQSPRHFAHF PASSSTVGALGEALTAGINVVPFTWAASPAATELEMVVVDWLGKALHLPETLLFA GGGGGTLLGTSCEAILCALVAARDRKLAEIGGRRIGDLVVYCSDQTHFAFRKAAR IAGILREHIREIQTCHANMFALSATALEAAMQADVEAGLVPLFVCATVGTTQTTAV DPIGELCTVTAPHGVWVHVDAAYAGSALVCPEFRHVINGVESVDSFSMNAHKWL 4904-4134-6834, v.1 CELB-010-W01 -78- ALKMWLVLRCYGIDGLREHIRSHVRMAEAFENLVRADERFEVVTDRQFALVCFR LRSPEKYGGEKTANELNRSLLEEVNAVTLGPYMSSANVGGMYMLRCAVGSTLTE DCHVTDGWKVVQDRATSILRKMEIIYSVLG >TDC008 (SEQ ID NO: 4) MAPPSQCLDAMHGAAHNGTAPAVADTKPQCPTVLDADVFRRQGHQVIDFIAEYY GGMGDYPVHPSVTPGFLRNVLPAEAPSRPEPDAFGSALRDVRDLILPGMTHWQS PRHFAHFPASSSTVGALGEALIAGINVVPFTWAASPAATELEMVVVDWLGKALHL PESLLFAGGGGGTLLGTSCEAILCALVAARDKKLAEIGERRIGDLVVYCSDQTHFA FRKAARIAGILRDHCRAIQTCREDMFALSPTELQAAMQADVDAGLVPLFLCATVG TTQTTAVDPIGKLCTVAASHGVWVHVDAAYAGSALVCPEFHHVIDGVEAVDSFS MNTHKWLLANNDCCAMWVKRPCELIAALGTEQEYILKDAASEGHDVVDYKDW TMTLTRRFRALKMWLVLRCYGVDGLRDHIRSHVRMAEAFEDMVRADERFEVVT DRQFALVCFRLQSPEKFGGEKTANELNRGLLEEVNAVGPGPYMSSANVGGVYML RCAVGSTLTEEHHVTDAWKVVQDRASVILRKMEIIYSVLG >TDC009 (SEQ ID NO: 5) MAPPPQHCFDTVNGATNNGVVVPVVMVDTPKQKLPCLTLLDADEFRRQGHQVI DFIADYYGRMGDYPVHPSVTPGFLRNQLPGAAPARPEPDAFGSALRDFRDLILPGI THWQSPRHFAHFPASSSTVGALGEALTAGINVIPFTWTASPAATELEMVVVDWLG KALHLPDSLLFAGGGGGALLGTSCEAILCALVAARDRKLAEIGGKRIVDLVVYCS DQTHFAFRKAARIAGIQRDHCREIRTCHADMFALSPTELRDAMQADVDTGLVPLF LCATVGTTQTTAVDPIGELCAVAAPHGVWVHVDAAYAGSALVCPEFRHVIDGVES VDSFSMNAHKWLLANNDCCAMWVKKPCALIAALGTEQEYILRDSAASDVVDY KDWTMTLTRRFRALKVWLVLRCYGVDGLRDHVRSHVRMAEAFENMVKADGR FEVVTDRRFALVCFRLRPREEFGGEKTANELNRGLLAEVNAVSSGPYMSSANVG GMYVLRCAVGSTLTEERHVEDAWTVVQDRASAILQRMEIIYSVL >HCL1 (SEQ ID NO: 6) MEANKDQVKEFIFRSKLPDIYIANHLPLHTYCFEKLSQFKDNPCLINGPTGDIYTY ADVELTSRKVASGLYKFGLQQGDVILLLLQNSPEFVFAFLGASFIGAISSTANPFYT SAEIAKQATASKAKLIITQAAFAEKVQQFAQENDHVKIMTIDSLTDNCLHFSELTSS DENEIPAVKIKPDDVVALPYSSGTTGLPKGVMLTHKGLVTSVAQQVDGENPNLYF HERDVILCVLPLFHIYSLNSVFLCGLRAGSAILLMQKFETVALMDLVQKYKVTIAP LVPPIFLAIAKSPVVDQYDLSSIRTVLSGAAPMGKELEDTVRAKLPNAKLGQGYG MTEAGPVIAMCLAFAKEPFEIKSGACGTVVRNAEMKIVDPETGDSQPRNKAGEIC IRGSQIMKGYLNDPEATERTIDKDGWLHTGDIGYIDEDELFIVDRLKELIKYKGFQ VAPAELESMLIAHPSISDAAVVPMKDEAAGEVPVAFVVRSNGSKITEDEIKQYISK QVIFYKRIGRVFFTEAIPKAPSGKILRKDLRAMVSAGDIPHQIPNMTYMQNQH 4904-4134-6834, v.1 CELB-010-W01 -79- >HCL2 (SEQ ID NO: 7) MPMETETNQGDLIFRSKLPDIYIPKHLPLHSYCFENISEFSSRPCLINGANNHIYTY ADVELTSRKVAAGLNKLGIQQKDTIMILLPNSPEFVFAFMGASYLGAISTMANPLF TPAEVVKQAKASNAKLIITQACFVNKVKDYAFDNNLNVICIDSAPEGCIHFSELTQ ADEHDIPDVKIQSDDVVALPYSSGTTGLPKGVMLTHKGLVTSVAQQVDGENANL YMHSEDVLMCVLPLFHIYSLNSVLLCGLRVGAAILIMQKFDIVQFCELIEKYKVTI GPFVPPIVLAIAKSPVVDNYDLSSVRTVMSGAAPLGKELEDAVRIKFPNAKLGQG YGMTEAGPVLAMCLAFAKEPFDIKSGACGTVVRNAEMKIVDPDTGCSLPRNQPG EICIRGDQIMKGYLNDPAATTRTIDKEGWLHTGDIGYIDNDDELFIVDRLKELIKY KGFQVAPAELEALLLNHPNISDAAVVPMKDEQAGEVPVAFVVRSNGSDITEDEVK DFVSKQVIFYKRIKRVFFVETVPKSPSGKILRKDLRARLAAGVPN >HCL3 (SEQ ID NO: 8) MANGIKKVEHLYRSKLPDIEISDHLPLHSYCFERVAEFADRPCLIDGATDRTYCFSE VELISRKVAAGLAKLGLQQGQVVMLLLPNCIEFAFVFMGASVRGAIVTTANPFYK PGEIAKQAKAAGARIIVTLAAYVEKLADLQSHDVLVITIDDAPKEGCQHISVLTEA DETQCPAVKIHPDDVVALPYSSGTTGLPKGVMLTHKGLVSSVAQQVDGENPNLYF HSDDVILCVLPLFHIYSLNSVLLCALRAGAATLIMQKFNLTTCLELIQKYKVTVAPI VPPIVLDITKSPIVSQYDVSSVRIIMSGAAPLGKELEDALRERFPKAIFGQGYGMTE AGPVLAMNLAFAKNPFPVKSGSCGTVVRNAQIKILDTETGESLPHNQAGEICIRGP EIMKGYINDPESTAATIDEEGWLHTGDVEYIDDDEEIFIVDRVKEIIKYKGFQVAPA ELEALLVAHPSIADAAVVPQKHEEAGEVPVAFVVKSSEISEQEIKEFVAKQVIFYK KIHRVYFVDAIPKSPSGKILRKDLRSRLAAK >HCL7 (SEQ ID NO: 9) MGERRFSNQQIDRLLRPKSVAVIGASDRKGALGATLLNNLVQYEFSGDIYPVNPK RDELLGLKVYHEVAELPEGIDCAVLAIPRPFVIDTVRQLAQRGCGAVVIYSAGFSE AGEEGMKDQLELAAIAAEYGMVIEGPNCLGCTNYVERVPLTFVETNMQTPPKGT RAVGIASQSGALAAVLATALHPRGLYVSSSVSTGNEAASGVEDYVEWLVDDEDT HVIAMYVESLRRPKAFIAAARRAHAAGKPIVMLHPGKSNKAQESAATHTGAMA GDYALMKTKLAREGVIFADTLEELADITEIALRCRALPGANMAVLGESGALRGLA FDIAEDIGLDLIHLDDDNSPALRAILPDFVPVSNPTDITALGLSEPEIYTKVLTALLE DERIGSVVASIIQSDPITSGIKFPHIIKVLDGGTFAKPLVFAGVDEGATVPKEYIDGL RKVGIPWFPSTERAYRAIARLADLSKRDLADNSGDPIVVPGLDAVSGVVPEYKAK ELLRPLGIAFPPSQFAANAEAAAAAARAIGYPVVMKAQAAALGHKSDAGGVILN LKTDDEVRDAFARIYGNVEAYDRSIALDGVLIEKMGKMGTEMIVGAKNDPQWG PVVLAGFGGVTAEILKDVKLFTPEMDAAAVQRGLLELKQAPILKGYRGAPALDV AALAELIVQIGRVMAGNPSIREIDLNPVIIHPAGEGVAALDALMLVER >HCL8 (SEQ ID NO: 10) MRNQGLGSWPVRRARMSPHATAVRHGGTALTYAELSRRVARLANGLRAAGVRP GDRVAYLGPNHPAYLETLFACGQAGAVFVPLNFRLGVPELDHALADSGASVLIHT 4904-4134-6834, v.1 CELB-010-W01 -80- GAMLTHGNLTWNCVNVLVETDLASDERALVAAPLFHAAALGMVCLPTLLKGGT VILHSAFDPGAVLSAVEQERVTLVFGVPTMYQAIAAHPRWRSADLSSLRTLLCGG APVPADLASRYLDRGLAFVQGYGMTEAAPGVLVLDRAHVAEKIGSAGVPSFFTD VRLAGPSGEPVPPGEKGEIVVSGPNVMKGYWGRPEATAEVLRDGWFHSGDVATV DGDGYFHVVDRLKDMIISGGENIYPAEVENELYGYPGVEACAVIGVPDPRWGEV GKAVVVPADGSRIDGDELLAWLRTRLAGYKVPKSVEFTDRLPTTGSGKILKGEVR RRFG >HCL9 (SEQ ID NO: 11) MKVNLGIGSYPRRRATVRPESTAIEFEGTSITYGEFSKRVNRLGHALLDLGVAHQD RVAYVGFNHPALLEVFFSTNLIGATPVLVNPRLSANEIDYIIQDSGASIVFYGIDLIE HATYLQELHPEIIMVAVEGDEGPGLRRKALIEAASDADIDLEVSDDDIALLMYTSG TTGRPKGAMLSHRNLFFNYFNALLSQEIEQGAVLLSTAPLFHIAGLNMTTIPVMM KGGKVIIHREFRAEHVLDEIERSKVSESFMVPAMIDMLSNHPSFAERDLSSLRAIM VGGSPLSERALRIWQGRDVKIVQGFGMTETAPGACILEATDTSTHLGTAGRAHFF TDIKLVDPKTGEEVPTGEAGEVLIRGPHVMTGYWNRPEDTASALQNGWYHSGDI AIKDEDGYYTIKDRIKDMYISGGENIYPAEVEQALQELEAVLDAAVIGVPDERWG ETGIAFVSIRESYLTNPPTGPELRELLGSVLARYKLPREIHIIEELPRNATGKIQKNIL RDFTIPVS >HCL11 (SEQ ID NO: 12) MLSVAEAQNSELSSHALPQTQASKETADHIFVSKLPSISIANHLPLHTYCFQNLSQF ADRQCLISGNNGKSYSFADTHLICRKVAAGLTKLGISKGDVIMVLLQNCAEFVFSF IGASMIGAVTTTANPFCTSKEIFKQFNASRSRLIVTQSQYVDKLRDTGDDSVVFGE DFAVVTIDAPPEGCLDFSVLCEADEADAPDVEIDPNDAVALPFSSGTTGLPKGVILT HKSLITSIAQQVDGENPNLYLKPDDVVLCVLPLFHIYSLNSVLLCSLRAGAGVLL MQKFEIGSLLELIQKHRVSVAAVVPPLVLALAKNPLVDSFDLSSIRLVLSGAAPLGK ELEAALLSRLPQAVFGQGYGMTEAGPVLSMSPLFAKQPLPTKSGSCGNVVRNAE LKVIDPETGCSLPRTQPGEICIRGPQIMKGYLNDAEATARTIDVDGWLHTGDIGFV DEDDDIFIVDRVKELIKFKGFQVPPAELEALLISHSQISDAAVVPQKDEAAGEVPVA FVVPAAGCELTEEAVKEFISKQVVFYKRLHKVFFVHAIPKSPSGKILRKDLRAKLA APSSTS >HCL12 (SEQ ID NO: 13) MAPQEQAVSQVMEKQSNNNNSDVIFRSKLPDIYIPNHLSLHDYIFQNISEFATKPC LINGPTGHVYTYSDVHVISRQIAANFHKLGVNQNDVVMLLLPNCPEFVLSFLAAS FRGATATAANPFFTPAEIAKQAKASNTKLIITEARYVDKIKPLQNDDGVVIVCIDDN ESVPIPEGCLRFTELTQSTTEASEVIDSVEISPDDVVALPYSSGTTGLPKGVMLTHK GLVTSVAQQVDGENPNLYFHSDDVILCVLPMFHIYALNSIMLCGLRVGAAILIMPK FEINLLLELIQRCKVTVAPMVPPIVLAIAKSSETEKYDLSSIRVVKSGAAPLGKELE 4904-4134-6834, v.1 CELB-010-W01 -81- KIVDPDTGDSLSRNQPGEICIRGHQIMKGYLNNPAATAETIDKDGWLHTGDIGLID DDDELFIVDRLKELIKYKGFQVAPAELEALLIGHPDITDVAVVAMKEEAAGEVPVA FVVKSKDSELSEDDVKQFVSKQVVFYKRINKVFFTESIPKAPSGKILRKDLRAKL ANGL >HCL13 (SEQ ID NO: 14) MTTQDVIVNDQNDQKQCSNDVIFRSRLPDIYIPNHLPLHDYIFENISEFAAKPCLIN GPTGEVYTYADVHVTSRKLAAGLHNLGVKQHDVVMILLPNSPEVVLTFLAASFI GAITTSANPFFTPAEISKQAKASAAKLIVTQSRYVDKIKNLQNDGVLIVTTDSDAIP ENCLRFSELTQSEEPRVDSIPEKISPEDVVALPFSSGTTGLPKGVMLTHKGLVTSVA QQVDGENPNLYFNRDDVILCVLPMFHIYALNSIMLCSLRVGATILIMPKFEITLLLE QIQRCKVTVAMVVPPIVLAIAKSPETEKYDLSSVRMVKSGAAPLGKELEDAISAK FPNAKLGQGYGMTEAGPVLAMSLGFAKEPFPVKSGACGTVVRNAEMKILDPDT GDSLPRNKPGEICIRGNQIMKGYLNDPLATASTIDKDGWLHTGDVGFIDDDDELFI VDRLKELIKYKGFQVAPAELESLLIGHPEINDVAVVAMKEEDAGEVPVAFVVRSK DSNISEDEIKQFVSKQVVFYKRINKVFFTDSIPKAPSGKILRKDLRARLANGLMN >HCL14 (SEQ ID NO: 15) MTERRFTNQQIDRLLRPKSVAVVGASDRTGALGATLLNNLVQYEFAGEIYPVNPK RDELLGLKVYHSVEELPEGIDCAVLAIPRPFVLDTVRQLAARKCGAVVIYSAGFSE AGEEGMKEQLELGAIAAEHGMVIEGPNCLGCTNYIARVPLTFVETNMRTPPKGTR AVGIASQSGALAAVLATALHPRDLYVSISVSTGNEAASGVEDYVEWLVDDEDTHV IAMYVESLRRPQAFIAAARRARAAGKPVVMLHPGKSDKAQASAATHTGAMAGD YALMKTKLAREGVIFADTLEELADITEIALRCKALPGANMAVLGESGALRGLAFD IAEDIGLDLIDLNDDNSPALRALLPDFVPVSNPTDITALGLSEPDIYTKVLTALLEDE RVGSVVSSIIQSDPITSGIKFPHIIKVLEDGTFPKPLVFAGVDEGANVPKEYIDGLRK VGIPWFPSTERAYRAIARLADLAKRDLTDRSAPPIAVPGLDAVSGVVPEYKAKELL SPLGIPFPESRFAASAEEAATAAEAIGFPVVMKAQAAALGHKSDAGGVILNLKSA EEVREAFTRIHANVGAYDTSIRLDGVLIEKMGRMGVEMIVGAKNDPQWGPVVL AGFGGVTAEILKDVKLFTPDLDEAAVHRALLGLKQAPLLTGWRGSPALDVAALA ALIVRVGRIMTGNPAIREIDLNPVIVHPEGEGVLALDALMLVD >HCL15 (SEQ ID NO: 16) MSTKRFTNQQIDRLLRPKSVAVVGASDRHGALGATLLNNLVQYEFAGDIYPVNPK REEIAGLKCYPTVDELPEGIDCAVLAIPRPFVLDTVRSLAARGCGAVVIYSAGFSE AGEEGLKEQLELGAIAAEHGMVIEGPNCLGCTNYVDRVPLSFVETNMLTPPAGA RAVGIASQSGALAAVLATTLHPRGCYVSTSVSTGNEAAAGVEDFVEWLVDDANT HVIAMYVESLRRPAAFVAAARRARAAGKPIVMLHPGKSNRAQESAATHTGAMA GDYALMKTKLAREGVIFADTLEELADITEIALRCKALPGANMVVLGESGALRGL AYDIAEDIGLDLLDLNDDNSPKLRALLPDFVPVSNPTDITALGLSEPEIYTKLLTAL LEDERVGSVVASIIQSDPITSKIKFPAIIKVLEAGTFAKPLVFAGVDEGARVPEEYIEG 4904-4134-6834, v.1 CELB-010-W01 -82- KELLAPLGLPFPQSRFAATADAAAAAAESIGFPVVLKAQAAALGHKSDAGGVILK LNSADEVRAAFDKIFSNVSAYDAAIRLDGVLVEKMGTMGVEMIVGAKSDPEWG PVVLAGFGGVTAEILKDVVLVTPDLSQAQVEEKLLGLRQAALLKGYRGSPELDV PALAKLIVEVGRIMAGNPAIREIDLNPVIVHSKGQGVVALDALMLVER >HCL16 (SEQ ID NO: 17) MTERRFTNQQIDRLLRPKSVAVIGASDRKGALGATLLNNLVQYEFAGDIYPVNPK RDELLGLKVYHTVDELPEGIDCAVLAIPRPFVLDTVRQLAARKCGAVVIYSAGFS EAGEEGMRDQLELASIAAEHGMVIEGPNCLGCTNYVERVPLTFVETNMQTPPKG ARAVGVASQSGALAAVLATALHPRGCYVSTSVSTGNEAASGVEDYVEWLIDDED THVIAMYVESLRRPKAFVAAARRARAAGKPIVMLHPGKSNKAQESAATHTGAM AGDYALMKTKLAREGVIFADTLEELADITEIALRCPALPGANMAVLGESGALRGL AFDIAEDIGLDLIDLNDDNSPALRAVLPDFVPVSNPTDITALGLSEPEIYTKVLTALL EDERVGSVVASIIQSDPITSGIKFPHIIKVLEDGSFPKPLVFAGVDEGATVPEDYIAG LRKVGIPWFPSTERAYRAIARLADLAKRDLTDRSAEPIAVPGIDSVAGVVPEYKSK ELLRPLGLAFPDSKFAASADEAVAAAEAIGYPVVMKAQAAALGHKSDAGGVILN LKSGDDVREAFGRMYANVGAYDASILLDGVLVEKMGRMGTEMIVGAKNDPEW GPVVLAGFGGVTAEILKDVKLFTPDMDQASVHAGLLELKQAALLKGYRGSPALD IAALAGLIVQIGRVMAGNPSIREIDLNPVIIHPEGEGVVALDALMLVD >HCL17 (SEQ ID NO: 18) MSGKRFTNKQIDRLLRPKSVAVVGASDRHGALGATLLNNLVQYEFAGDIYPVNP KREEIQGLKCYASVDQLPEGIDCAVLAIPRPFVLDTVRSLAKRGCGAVVIYSAGFS EAGEEGMKEQLELGAIAAEYGMVIEGPNCLGCTNYVERVPLTFVETNMITPPKGA RAVGIASQSGALAAVLATALHPRGCYVSTSVSTGNEAASGVEDYVEWLIDDEDT HVISMYVESLRRPKAFIAAARRARAAGKPIIMLHPGKSNKAQESAATHTGAMAG DYALMKAKLGREGVIFADTLEELEDITEIALRCPSLPGANMAVLGESGALRGLAF DIAEDIGLDLIDLNDDNSPALRAVLPDFVPVSNPTDITAAGLSEPEIYTKVLTALLA DERVGSVVASIIQSDPITSKIKFPAIIKVLEDGSFAKPLVFAGVDEGARVPQEYIDGL RAVGIPWFPSTERAYRAISRLADLAKRDLSDNSQAPLPVPALKGVSGVVPEYKAK ELLAPLGIPFPQSKFAATADDAAAAAEEIGFPVVLKAQAAALGHKSDAGGVILKL DSAEAVKAAFDKIFTNVAAYDASIQLDGVLVEKMGTMGMEMIVGAKSDPEWGP VVLAGFGGVTAEILKDVVLLTTDLSEEQVAAKLLTLKQAALLKGYRGSPELDVPA LAKLIVEIGRVMEGNPSIREIDLNPVIVHPKGQGVVALDALMLVQH >HCL18 (SEQ ID NO: 19) MSERRFTNEQIDRLLRPKSVAVIGASDRKGALGATLLNNLVQYEFDGDIYPVNPK RDELLGLKVYHTVDELPEGIDCAVLAIPRPFVLDTVRGLAARKCGAVVIYSAGFS EAGEEGMKEQLELGEIAREHGMVIEGPNCLGCTNYVERVPLTFVETNMQTPPKG TRAVGIASQSGALAAVLATALHPRGCYVSTSVSTGNEAASGVEDYVNWLVDDED THVIAMYVESLRRPKAFIEAARRARAAGKPIIMLHPGKSNKAQESAATHTGAMA 4904-4134-6834, v.1 CELB-010-W01 -83- FDIAEDIGLDLIDLNDDNSPALRAVLPDFVPVSNPTDITAIGLSEPEIYTKVLTALLD DDRVGSVVASIIQSDPITSGIKFPHIIKVLEDGSFAKPLVFAGVDEGATVPQEYIDGL RKVGIPWFPSTERAYRAIARLADLAKRDLTDQSGEPLPLSGMAEVSGVVPEYKAK ELLRPAGIAFPESKFAPSADEAAAVAETIGFPVVMKAQAAALGHKSDAGGVILNL KTADEVREAFTRMYDNVASYDSSITLDGVLVEKMGRMGTEMIVGAKSDPQWGP VVLAGFGGVTAEILKDVKLFTPDMGVERVKEGLLALKQAPILKGYRGSPELDVD ALADLIVKIGQVMTGNPSIREIDLNPVIIHPKGDGVVALDALMLVD >THT1 (SEQ ID NO: 20) MASAISETITTNGPSENNNLTITGKIHTRVRLATKSDLHHIYQLFYQIHAYHNFTHL YKATESSLGDLLFKENPLPLFYGPSVLLLEVSPTPFTQPKNNKDEGFKPVLTTFNL KFPVVEGQVEEFQSKYDDGNDKRDVFIAGYAFFYANYSCFYDKPGFYFESLYFRE SYRKLGMGRLLFGTVASIAANNGFVSVEGIVAVWNKKSYDFYIDMGVEIFDEFRY GKLHGENLQKYADKQKNEGGNC >THT2 (SEQ ID NO: 21) MATTNNKNLTITEKVYVRVRLANEADISHIYKLFYQIHEYHNYTHLYKATESSLC DLLFKANPNPLFYGPSVLLLEVSPTPFENTKKDEKFKPVLKTFDLRATVEDKEAE EFKSKSCGDEKEDVFIAGYAFFYANYSCFYDKAGIYFESLYFRESYRKLGMGSLLF GTVASIAANNGFASVEGIVAVWNKKSYDFYVNMGVEIFDEFRYGKLVGDALQKY ADKEKA >THT3 (SEQ ID NO: 22) MAAVTVEITRSEVLRPSPASAGGGEMVPLTVFDRAATDGYIPTMFAWDAAAAAA LSNDAIKDGLAAVLSRFPHLAGRFAVDERGRKCFRLNNAGARVLEASAAGDLAD ALAHDVAAHVNQLYPQADKDRVDEPLLQVQLTRYTCGGLVIGAVSHHQVADGQS MSVFFTEWAAAVRTAGAALPTPFLDRSAVAAPRIPPAPAFDHRNVEFRGEGSRSHS YGALPLERMRNLAVHFPPEFVAGLKARVGGARCSTFQCLLAHAWKKITAARDLS PKEYTQVRVAVNCRGRAGPAVPTDYFGNMVLWAFPRMQVRDLLSASYAAVVGVI RDAVARVDERYIQSFVDFGEVAAGDELAPTAAEPGTAFCPDLEVDSWIGFRFHDL DFGGGPPCAFLPPDVPIDGLLIFVPSCAAKGGVEMFMALDDQHVEALRQICYSM D >THT17 (SEQ ID NO: 23) MAPALQLPTLSETIITDASLENNNVTITRKIYTRVRLATKSDLSHIYQLFYQIHVYH NYTHLYKATESSLSNLLFKENPLPLFYGPSILIVEVSPTPFKEPKNTTNGGFKPVLT TFDLKFPVVEGQVEEFRSKYDDKSDVYIAGYVFFYANYSCFNDKPGLYLESLYLR ESYRKLGMGKLLFGTVSSIAANNGFVSLEEIVAVWNKKAYDLYVNMGLEIFDEFR YGKLHGENLQKYAHILWRQLIVN 4904-4134-6834, v.1 CELB-010-W01 -84- >THT18 (SEQ ID NO: 24) MAPALQQPTPTETITIDASSENNNVTITGKIYTRVRLATKSDLSHIYQLFYQIHEYH NYTHLYKATESSLANLLFKENPLPLFYGPSVLLLEVSPTPFNEPKNTTNEGFKPVL TTFDLKFPVVEGQVEEFRSKYDDKSDAYIAGYAFFYANYSCFYDKPGFYFESLYF RESYRKLGMGSLLFGTVASIAANNGFVSVEGIVAVWNKKSYDFYINMGVEIFDEF RYGKLHGENLQKYADKKEKNDEGTT >THT19 (SEQ ID NO: 25) MGTIEKNLTITEKVYVRVRLANENDIHHVYKLFYQIHEYHKFTHLYKATESSLCD LLFDKTNPKPLYYGPSVLLLEVSPTPFSDIDNKDEKFKPVLKQFDLRANVVDKEA DEFKSKSCAHDEKNDVYIAGYAFFYANYSCFYDKAGIYFESLYFRESYRKLGMGS LLFGTVASIAANNGFSSVEGIVAVWNKKSYDFYVNMGVEIFDEFRYGKLVGDALQ KYADKEKV >THT20 (SEQ ID NO: 26) MASAPQPPTLSEKTTNLSPENNNVTITGKIYTRVRPATKSDLHHAYQLFYQIHAYH NQFHLFKATESSLSDLLFKENPLPLFYGPTLLLLEVSPTAFTEPKNNKDEGFKPVV TALDLKFPVVEGQVEEFRSKYDDGTDKRDVFIAGYAYFFASYSLFGNDKPGIHFD SLYFRESYRKLGMGKLLFGTVASIAANNGFAALEGIIAVWNKKSYDFYVSMGVEI DDDFRFGKLDGENLQKYADKEKNGAGSC >THT22 (SEQ ID NO: 27) MEITAAMVKPVYSTPHPLVGEKVPLTVFDRAASDLFVPTVFAYPAPAPSNEALKE GLRKALAPYTHLAGRLAVDDRGRRFVHVNDEGVLVVEAALSADLSDVISKGMP AGNVDKLYPTLPEENVGAALLQIKLNRYKCGGLVIGIICHHHVADGHSMSTFFTT WASAVRAGKDFTFPSPPFLDRAATAVPRGTPAPVLDHWSIEFNRSGHGRSSRQYAV VPMDKIKNLTVHFTPDFVAELKARVGVRCSTFQCLLAHVWKKITAARGLEPEEFT QLRVSVNCRSRADPAVPMDFFGNMVLWAFPRLQVRDLLNSSYGRVVHAIRDAVA RIDGEYIQSFVDFGAVADASGEELVETAATAGTMLCPDLEMDSWLGFQFHQMDL GSGPPCAFLPPDLPIEGLVLFVPSRATKGGVDLFMAVADCHAEAFEQICHSVD >THT23 (SEQ ID NO: 28) MAVPVEITRRALLRPREACDHAGGRTIPLTVFDRASTDGYVPAVFAWTAQGAPTN AALVDGLLATLARFPHLAGRLGVDDRGRRCFHLNNSGVIVFEAVAAADLADALA HDVSEHIDQLFPKADEERCPDEPLLQVQLTRYRCGGLVIGTACQHHVADGQSMSF FYAAWATAVSTGLAVLPSPFIDRMAAVVARSPPEPAFDHRNIEFMGEHNPSRSYPV VPRDRIKNLTVNFPEEFVARLKARVAARCSMFQCLLAHAWKKVTEARCLAPEELT QVRVAVNCRSRAKPPMPMDFFGNMVLWAFPRMRAGELLSSSYAAVIGVIRDAVV RVDAEYVQSFVDFGEALERSGEELTATAAVVGTAFCPDLEVDSWLGFGFHDLDFG GGPPCAFLPPVLPVEGLMFFVRSCTAKGGVDLFAALHDEHVDAFKQICYSLD 4904-4134-6834, v.1 CELB-010-W01 -85- >THT24 (SEQ ID NO: 29) MAVTVEITRRAVVRPPPEIARGGGRRLPLTAFDRASTDGYISAVFAWNAPAPDNAA LVDGLLAAVARYPHLAGRLGVDDETSRRCFHLNDAGVLVIEATADADLADALAV AVHVNDLYPKANKERGADDDQPLFQAQLTRYTCGGLVIGTACQHLVADGQSMSF FYTAWATAVRTASSATIPTPFTDRAAIAVPRNPPTPKFDHRNIEFRGEHHSLSHSYGT LPMDRIKNLAIHFPEEFIAGLKSRVGGGRCSTFQCLLAHAWKKVTAARDLSPEVF TQVRVAVNCRSRANPPVLMEYFGNMVLWAFPRMTAREVVTSSYAAVAGAIRDAV ARVDAEYVQSFVDFGEVAERDGEELASTAAGPGMAFCPDLEVDSWLGFRFHDLD FGHGPPCAFLPPDLPIEGVMILVPSCSAKGGIDLFLALDDEHVEAFKQICYSMD >THT25 (SEQ ID NO: 30) MAMAVEITRSEVLRPSPASGGGEMVPLTAFDRAATDGFIPTMFAWDGAAAAALS DDAIKDGLAAVLARFPHLAGRFDVDELGRKCFRLNDAGAWVLEASAAGDLADA LAHDVAAHVNELYPQANERADEPLLQVQLTRYTCGGLVIGVVSHHQVADGQSMS VFFTEWAAAVRTGGATLPTPFVDRAAVAAPRSPPEPAFDHRNIEFKGEQSRSHSYG SLPLDRMRNIAVQFPAEFVAGLKAQVGARCSTFQCLLAHAWKKITAARDLSPEEF TQVRVAVNCRGRASPAVPMDYFGNMVLWAFPRMQVRDLLSSSYATVVGAIRDAV ARVDEQYIQSFVDFGEVAIDDELVPTAAEAGTVFCPDLEVDSWLGFRFHELDFGG GPPCAFLPPDLPVEGMLIFVPSCSAKGGVEMFMALDGHHVDALSQICYSMD >THT26 (SEQ ID NO: 31) MAIGLINNTILKAHSSFASSLHIPAEDVIIPLTIFDKAAFDLHVAVLYAFKPPMPSNE VLKDALSKVLVYYPHLAGRFITDDLGRTCIILNNAGVRITETYIATTLTEQLPFNPS KDVSHLLPPVEGVEELFQIQLNRYACGGLVIGETSHHRVADGQSMSSFFVAWARM VRGLDLESLPYHDRFAVSQPRNPPTVEFDHPSIEFKKTTVNPDTTPIFSSIETLIINYS TEFINKLKAKVLGENCNPHQRYSTFECLLSHTWKKVTQARGLDLEESTQVRVAV NGRARIKPAVPMEYFGNLVLWAYPTLKVKELLQESHAYVSKAIHDEVIRVDSRYF KSFIDFGAAKENVDNEGDDLESTAPEFGNTLCPNLEVDSWLRFQFHDLDFGGGSP CAFFPPNIPVEGLIIFLPTCSEDGGVDVVISLLPEHVPLFKQISHSMDY >THT27 (SEQ ID NO: 32) MSVKVISSTTLYPSPSSDPSICYDTKIPLTIFDKAAFDLNVSVLYVFQPPMPSNEAL KAGLLKALVHFPHLAGRLTTDEQGRPCIHLNNAGVRVIETYIPVTLAEQLPFNPNT DIEDLFPPIEGFEEIMQIQLNRYACGGLVIGQTCHHHVGDGQSMSSFYFTWAKLVR AAGLASNKIDQDPIILPYHDRASVAVPRNPPNVEFDHRSIEFRKTSKENVRSSSSIK NLVVNFSVDFIAKLKMKVNEEISNCTTNSLPPHKMYTTTFECLLAHVWKKVTQA RGLEQDEFTQVRVAVNGRARMKPTVPMEYFGNLVLWAYPRLQVKELLQENYAY VAGAIHEAVAQVDNNYFKSFIDFGEVAKEDGGEKLVAMAPDIGNLLCPNLEVDSW LRFQFHHMDFGGGSPCAVLPAELPVEGLVIFVPSCKEGGGIDVVMALQHEHVQIF KDICHLY >THT31 (SEQ ID NO: 33) 4904-4134-6834, v.1 CELB-010-W01 -86- YKTTESSLGDLLFKENPLPLFYGPSVLLLEVSPTPFTQPKNNKDELGFKPVLTTFD LKFPVVEGQVEEFQSIYDDGNDKRDVFIAGYAFFYANYSCFYDKPGFYFESLYFR ESYRKLGMGRLLFGTVASIAANNGFVSVEGIVAVWNKKSYDFYIDMGVEIFDEFR YGKLHGENLQKYADKEINDAGST >THT32 (SEQ ID NO: 34) MASAPQPPTLSEKTTNLSPENDNVTITGKIYTRVRLATKSDLHHAYQLFYQIHAYH NQFHLFKATESSLSDLFFKENPLPLFYGPTLLLLEVSPTAFTEPKNNKDEGFKPVFT ALDLKFPVVEGQVEEFRSKYDDGTDKRDVFIAGYAYFFASYSLFGNDKPGIHFDS LYFRESYRKLGMGKLLFGTVASIAANNGFAAVEGIVAVWNKKSYDFYVSMGVEM HDDFRFGKLDGENLQKYADKEKNGAGSC >CmT3H (SEQ ID NO: 35) MESLFLLAFSLLALIISVKLLYSKRFKLPPGPRPWPLFGNLHEIEPVRFRCFAKWAE RYGPIMSVWIGGSLNVIVSSPELAREVLKEQDQHLANRHRTRSAAKFSREGTDLI WADYGPHYVKVRKLCTLELFSVKRLEALRAIREEEVSAMVESLYTDCKGKSEER LVLRTYLSVVTFNHITRLVFGKRFINSKGEMEEQGKEFKDIVATGNELSASLSIAEH LPWLQSLFPLEVEAFDKHWDRRDRLTRTIMEEHTKARLESGSEQQHFVGALLSLR DEYDLSDDTVTGLLWDMIQAGMDTIAITCEWGMAELIRNPQVQAKAQEELDRVI GDKRAMTESDFSQLPYLRCIAKESLRLHPPTPLMLPHRASKHIKLGGYDVPKGSN VHVNAWAIARHPDTWKDPTVFRPERFLEDDVDMKGQDFRLLPFGSGRRICPGAT LGTYLLQLMLGRMLHGFRWTTIDASSIDMSEDPGLVAFMTTPLVAVATPRLPSDLY SCQSMKV >AtATR2 (SEQ ID NO: 36) MSSSSSSSTSMIDLMAAIIKGEPVIVSDPANASAYESVAAELSSMLIENRQFAMIVT TSIAVLIGCIVMLVWRRSGSGNSKRVEPLKPLVIKPREEEIDDGRKKVTIFFGTQTG TAEGFAKALGEEAKARYEKTRFKIVDLDDYAADDDEYEEKLKKEDVAFFFLATY GDGEPTDNAARFYKWFTEGNDRGEWLKNLKYGVFGLGNRQYEHFNKVAKVVD DILVEQGAQRLVQVGLGDDDQCIEDDFTAWREALWPELDTILREEGDTAVATPYT AAVLEYRVSIHDSEDAKFNDINMANGNGYTVFDAQHPYKANVAVKRELHTPESD RSCIHLEFDIAGSGLTYETGDHVGVLCDNLSETVDEALRLLDMSPDTYFSLHAEK EDGTPISSSLPPPFPPCNLRTALTRYACLLSSPKKSALVALAAHASDPTEAERLKHL ASPAGKDEYSKWVVESQRSLLEVMAEFPSAKPPLGVFFAGVAPRLQPRFYSISSSP KIAETRIHVTCALVYEKMPTGRIHKGVCSTWMKNAVPYEKSENCSSAPIFVRQSN FKLPSDSKVPIIMIGPGTGLAPFRGFLQERLALVESGVELGPSVLFFGCRNRRMDFI YEEELQRFVESGALAELSVAFSREGPTKEYVQHKMMDKASDIWNMISQGAYLYV CGDAKGMARDVHRSLHTIAQEQGSMDSTKAEGFVKNLQTSGRYLRDVW >AmCPR1 (SEQ ID NO: 37) 4904-4134-6834, v.1 CELB-010-W01 -87- VFFFVWRRSLGQKSGKVVEVNKLVVVKPEQEAEVDPGKEKVTIFFGTQTGTAEG FAKALAEEAKARYDKAIFKVVDLDDYAADDDEYEEKLRKEKIAFFMLATYGDGE PTDNAARFYKWFIEGNDRGIWLQNVKYGVFGLGNRQYEHFNKVAKQVDEKLFE QGANRLVPVGLGDDDQCIEDDFTAWREILWPELDKLLRGDDDAPAVSTPYTAAVP EYRVIFLDSADAVHEDKYSTMANGHAVHDIQHPCRANVAIRRELHTPASDRSCIH LELDISGTGLMYETGDHVGVFADNGTEIAEEAEKLLGYSPETFFSIHTDKEDGTPL SGSSLPPPFPSPITLRKALSHYADLLNPPRKAALVALAAHAFDPSEAERLRFLASPI GKDEYSQWVVANQRSLLEVMAEFPSAKPPLGVFFAAIAPRLQPRYYSISSSPRMA PTRIHVTCALVEGPTPTGRIHRGVCSSWMKNSVPSEESRDCSAAPIFVRTSNFKLP ADSSIPIIMVGPGTGLAPFRGFLQERLALKEAGVELGPAILFFGCRNHRMDFIYED ELNNFVEQGVLSELIIAFSREGPTKEYVQHKMIDKASSLWEIISRGGYLYVCGDAK GMARDVHRTLHTIVQEQGSMESSPAEAMVKNLQTEGRYLRDVCFLH >AmCPR2 (SEQ ID NO: 38) MEKKPQRLLILYASQTGNALDVAEHVEREAGRRHCPAIVLSTDQFDARELPSEGT VCFIVSTTGQGDTPDSMKEFWRSLLQRNLSHQWLEGVYYAVFGLGDSGYQKYN VVAKKLDKRLTDLGAKPIIGKGLGDEQHPSGYEGDLDPWLSSFWVTLKKMHPSI FTCDTQLFDPNMKVLDYPKFQIIYHDVEKAPSYVSRNIDLNLMEIESVRTMTPGK FPHHDCRRQCFVNMAKNVRLTNEDGDRDVRLFEFNILSSDTEYEVGDVLEILPCQ NPAAVNAFLQRCNLDPESYISVQLADTAKSLPVSKLNISCKPIKLRTFVELTMDIAS ASPRRYFFEVMSFFATAEHEKERLQYFASPEGRDDLYQYNQKERRTVLEVLEDFP SVQMPFEWFVQLVPPLKTRLFSISSSPLAHPDQIHLTVAVVAWTTPFKRKRHGLCS TWLAGLDPQKETRIPAWIQRGSLRRPSPSLPLILIGPGTGCAPFRAFVEERALQSTQ GPVAPVIFFFGCRNQEKDFLYKDSWLSHCENSGVLSEEKGGGFFVAFSRDQLQKV YVQHKMREQSQRIWELLGEGGAVYIAGSATKMPADVMLALEEIITKEGGTPMES ATRLIRQLEKVGRYNVEAWS >OMT6 (SEQ ID NO: 39) MGSTAETQLTPVQVTDDEAALFAMQLASASVLPMALKSALELDLLEIMAKNGSP MSPTEIASKLPTKNPEAPVMLDRILRLLTSYSVLTCSNRKLSGDGVERIYGLGPVC KYLTKNEDGVSIAALCLMNQDKVLMESWYHLKDAILDGGIPFNKAYGMSAFEY HGTDPRFNKVFNNGMSNHSTITMKKILETYKGFEGLTSLVDVGGGIGATLKMIVS KYPNLKGINFDLPHVIEDAPSHPGIEHVGGDMFVSVPKGDAIFMKWICHDWSDE HCVKFLKNCYESLPEDGKVILAECILPETPDSSLSTKQVVHVDCIMLAHNPGGKE RTEKEFEALAKASGFKGIKVVCDAFGVNLIELLKKL >OMT7 (SEQ ID NO: 40) MGSTGNAETQLTPTHVSDEEANLFAMQLASASVLPMVLKAAIELDVLEIMAKSIP HGSGAYISPAEIAAQLPTTNPDAPVMLDRVLRLLASYSVVTCSLRELPDGKVERLY GLAPVCKFLTKNEDGVSLAPLCLMNQDKVLMESWYYLKDAILDGGIPFNKAYG MTAFEYHGTDPRFNKVFNRGMSDHSTITMKKIFEMYTGFEALNTIVDVGGGTGA 4904-4134-6834, v.1 CELB-010-W01 -88- DWSDEHCLKFLKNCYAALPEHGKVIVAECILPLSPDPSLATKGVIHIDAIMLAHNP GGKERTEKEFEALAIGAGFKGFKVACCAFNTYVMEFLKTA >OMT8 (SEQ ID NO: 41) MGSTGETQIIPTHVNDEEANLFAMQLASASVLPMILKSALELDLLEIIAKAGPNAQ LSPSNIAAQLPTKNPDAAVMLDRMMRLLACYNVLSCSVRTLPDGKIERLYGLAPV AKYLVKNEDGVSIAPLNLMNQDKVLMESWYYLKDAVLEGGIPFNKAHGMTSFE YHGKDLRFNKVFNKGMADHSTITMKKILETYTGFEGLTSLVDVGGGTGAVISMIV SKYPSINGINFDLPHVIEDAPSYPGVEHVGGDMFVSVPKADAVFMKWICHDWSD EHCVKFLKNCYDALPENGKVIVAECILPASPDSSLATKGVVHIDVIMLAHNPGGK ERTEKEFEALAKAAGFQGFRVCCSAFNTYIMEFLKKP >OMT9 (SEQ ID NO: 42) MGSTAADMAATADEEACMFALQLASSSILPMTLKNAIELGLLDTLVQASGKSLTP AEVAAKLPSSSNPAAPDMVDRMLRLLASYGVVSCAVEEGENGKLSRRYAAAPVC KWLTPNEDGVSMAALALMNQDKVLMESWYYLKDAVLDGGIPFNKAYGMSAFE YHGTDPRFNRVFNEGMKNHSIIITKKLLDLYPGFEGLGTLVDVGGGVGATVGAIV ARHPAIKGINFDLPHVISEGIPFPGVTHVGGDMFQKVPSGDAILMKWILHDWSDA HCATLLKNCYDALPAHGKVVIVECILPVNPEATPKAQGVFHVDMIMLAHNPGGK ERYEREFEELARGAGFTGVKATYIYANAWAIEFTK >OMT10 (SEQ ID NO: 43) MGSTGETQMSPAQILDEEANFALQLISSSVLPMVLKTAIELDLLEIMAKAGPGALL PPSDIASHLPTKNPNAPVMLDRILRLLASYSILICSLRDLPDGKVERLYGLASVCKF LTRNEDGVSVSPLCLMNQDKVLMESWYHLKDAILEGGIPFNKAYGMTAFEYHGT DPRFNKVFNKGMSVHSKMAMKKILETYKGFEGLASLVDVGGGTGAVVSTIVSK YPSIKGINFDLPHVIADAPAFPGVENVGGDMFVSVPKADAVFMKWICHDWSDEH CLTFLKNCYDALPENGKVILVECILPVAPDTSLATKGVMHVDVIMLAHNPGGKER TDREFESLARGAGFKGFEVMCCAFNTHVIEFRKKA >AML1.000 (SEQ ID NO: 44) MDQIEAMLCGGGEKTKVAVTTKTLADPLNWGLAADQMKGSHLDEVKKMVEEY RRPVVNLGGETLTIGQVAAISTVGGSVKVELAETSRAGVKASSDWVMESMNKGT DSYGVTTGFGATSHRRTKNGTALQTELIRFLNAGIFGNTKETCHTLPQSATRAAM LVRVNTLLQGYSGIRFEILEAITSLLNHNISPSLPLRGTITASGDLVPLSYIAGLLTGR PNSKATGPDGESLTAKEAFEKAGISTGFFDLQPKEGLALVNGTAVGSGMASMVLF EANVQAVLAEVLSAIFAEVMSGKPEFTDHLTHRLKHHPGQIEAAAIMEHILDGSS YMKLAQKVHEMDPLQKPKQDRYALRTSPQWLGPQIEVIRQATKSIEREINSVNDN PLIDVSRNKAIHGGNFQGTPIGVSMDNTRLAIAAIGKLMFAQFSELVNDFYNNGL PSNLTASSNPSLDYGFKGAEIAMASYCSELQYLANPVTSHVQSAEQHNQDVNSLG LISSRKTSEAVDILKLMSTTFLVGICQAVDLRHLEENLRQTVKNTVSQVAKKVLTT 4904-4134-6834, v.1 CELB-010-W01 -89- GETEKNAVTSIFQKIGAFEEELKAVLPKEVEAARAAYGNGTAPIPNRIKECRSYPLY RFVREELGTKLLTGEKVVSPGEEFDKVFTAMCEGKLIDPLMDCLKEWNGAPIPIC >C4H (SEQ ID NO: 45) MDLLLLEKSLIAVFVAVILATVISKLRGKKLKLPPGPIPIPIFGNWLQVGDDLNHRN LVDYAKKFGDLFLLRMGQRNLVVVSSPDLTKEVLLTQGVEFGSRTRNVVFDIFTG KGQDMVFTVYGEHWRKMRRIMTVPFFTNKVVQQNREGWEFEAASVVEDVKK NPDSATKGIVLRKRLQLMMYNNMFRIMFDRRFESEDDPLFLRLKALNGERSRLA QSFEYNYGDFIPILRPFLRGYLKICQDVKDRRIALFKKYFVDERKQIASSKPTGSE GLKCAIDHILEAEQKGEINEDNVLYIVENINVAAIETTLWSIEWGIAELVNHPEIQS KLRNELDTVLGPGVQVTEPDLHKLPYLQAVVKETLRLRMAIPLLVPHMNLHDAK LAGYDIPAESKILVNAWWLANNPNSWKKPEEFRPERFFEEESHVEANGNDFRYVP FGVGRRSCPGIILALPILGITIGRMVQNFELLPPPGQSKVDTSEKGGQFSLHILNHSI IVMKPRNC >YlAro4 (SEQ ID NO: 46) MSRSSSPNASSAEDVRILGYDPLLAPALLQTEVASTKNARETVSKGRKDSIDVITG KSDKLLCIVGPCSLHDPKAAMEYAQRLKELSDKLSGELVIVMRAYLEKPRTTVG WKGLINDPDMDESFNINKGLRLSRKVFCDLTDLGLPIASEMLDTISPQFLADLLSL GAIGARTTESQLHRELASGLSFPVGFKNGTDGTLGVAVDAVQAASHPHHFMGVT KQGVAAITTTKGNENCFIILRGGKKGTNYDAESVAECKKATESMLMVDCSHGNS NKDYRNQPKVSKAVAEQVAAGEKKIIGVMIESNIHEGNQKVPKEGPSALKYGVSI TDACVSWETTVDMLTELANAVKERRNKN >YlAro1 (SEQ ID NO: 47) MFAEGQIQKVPILGKESIHIGYKMQDHIVSEIVANIKSSTYILVTDTNIEDLGYVESL KTKFEAAFAKDGIKSRLLTYTVAPGETSKSRATKAAIEDWMLSKGCTRDTVILAV GGGVIGDMIGYVAATFMRGVRFVQIPTTLLAMVDSSIGGKTAIDTPLGKNLVGAF WQPVNIFIDTSFLETLPVREFINGMAEVIKTAAFYDAEEFTRLESASEIFLSTIKKRD AKDPRRVDLSPITDTIGRIVLGSARIKAAVVSADEREGGLRNLLNFGHSIGHAYEAI LTPYILHGECVAIGMVKEAELSRYLGILSPVAVARLAKCIKAYELPVSLDDATVKA RSHGKKCPVDDLLRIMGVDKKNDGSTKKIVILSAIGKTHEQKASSVADKDIRFVL SEEVIVGEAPVGDKKSYTVTPPGSKSISNRAFVLTALGKGPCKLRNLLHSDDTQH MLEAIELLGGASFEWEADGETLLVTGNGGKLTAPAQELYLGNAGTASRFLTTAAT LVQKGDKDHVILTGNKRMQERPIGPLVDALRSNGADIAFQNAEGSLPLKIEAGVG LKGGLIEVAATVSSQYVSSLLMCAPYAQTPVTLSLVGGKPISQFYIDMTIAMMAD FGVVVTKDETKEHTYHIPQGVYTNPEEYVVESDASSATYPLAYAAMTGHTVTVP NIGSKSLQGDARFAIDVLKAMGCTVEQTATSTTVTGVPNLKAIAVDMEPMTDAFL TACVVAAVSEGTTVITGIANQRVKECNRIEAMRVQLAKYGVVCRELEDGIEVDGI SRSDLKTPVSVHSYDDHRVAMSFSLLSSIMAAPVAIEERRCVEKTWPGWWDVLS 4904-4134-6834, v.1 CELB-010-W01 -90- LDQLLEKDLDTTIPQLIADKGWDHFRAEELRLLKQCLNDKSEGYVISCGGGVVET PAARDALQTFKGVGGIVLHVHRPVSRILEYLNKDQSRPAFVDDLEAVWQRRKEL YRSVSSNVFFAPHCDSAEATAKVQQMLGAFLDRVTGKSEFVIPHKDQFTSFLSLTF PDVSIAATMLPSLSEGCSALELRVDLLNENDEAIPSEEYVLSQLAILRQNVDLPILY TVRTKAQGGRFPDDKPVELANLVNLGLKTAVELLDVELTYPAELVSSVGASRGYT KLLGSHHDFPGALNWSSLEWENMYARAEAVPVDVVKLVGMAKSFSDNFALENF REAHTSSPLLAINMGSHGQLSRVTNTLLTPVTHADLPVAAAPGQLSVEEINQTRST IGMFNKNLSFFIVGTPIGHSKSPILHNTMFKKLGLPYEYSRFKTDDAAAVNAKAR ALLAQGNLGGISVTIPLKQDIIPFLDEVSPLAQQIGAVNTIIPGPNGTLKGDNTDILG LVNALTRFGANSLDKKTALIVGAGGTSLAAVHGLRSLGFAKILIANRTLSKAEAIA DKFDNVEAVTLDSFVANKYTPSVIVSCVPATTFSMLDESNKLVSAALAASPKGLV LEAAYSAEATPLLKQVMDVEGWEFISGLYMLTEQGFEQFRLWTGIPAPKEVGEKA VLGN >ChS (SEQ ID NO: 48) MSTFGTLFKVTTYGESHCKSVGCIVDGVPPGMDLDESDIQPQLTRRRPGQSALTT PRNERDAVAIQSGTEYGKTLGTPIAMLVQNKDQRPHDYSEMDDYPRPSHADYTY QEKYGIKASSGGGRSSARETIGRVAAGAIADKYLAAVNDIEIVAFVSQVGDVSMD RSPRNEQWISTLEGVTREGIDSTGPMRCPDLALGEKMVKIVEEHRDSHDSVGGV VTCVIRNCPVGLGEPCFDKLEATLAHAMMSIPATKGFEFGSGFAGAAMSGSKHN DMFYKDVASGRFRTRTNYSGGVQGGISNGENIYFNIAFKPPATISQEQATATYAGK DGVLAAKGRHDPNVVPRAVPIVEAMAALVIADAHLIQESRKGAKSFF >ChM (SEQ ID NO: 49) MDFTKADTVLDLANIRDSLVRMEDTIVFNLIERAQFCRSEFVYKAGNSDIPGFKG SYLDWFLQESEKVHAKLRRYAAPDEQAFFPDDLPEAILPPIDYAPILAPYSKEVSV NDEIKKIYTDDIVPLVCAGTGDQPENYGSVMVCDIETLQALSRRIHFGKFVAESKF LSETERFTELIKNKDIAGIEAAITNSKVEETILARLGEKALAYGTDPTLRWSQRTQG KVDSEVVKRIYKEWVIPLTKKVEVDYLLRRLE >PHA2 (SEQ ID NO: 50) MSIEEWKKTKLVGVIGMGDMGRLFANHWNSQGWKVLACDQESHYEKLKEEFA DSEIEIVQNGHYVSRKCDYILYCVEAENIGKIVSIYGPSTKVGSIVGGQTSCKAPE MAAFEAHLPSDVDIISCHSLHGPKVNPEGMPLVIIRHRNTEEWKFEFVQSLLESLK SKIVYLSAEQHDKITADTQAVTHAAFLTMGKAWQANGQYPWQISRWIGGLENAK MNISLRIYSNKWHVYAGLAISNPAAKVQIQQYASSAGDLYKLMITGKEQELLDRL TAARDFVFGGLKKEHSLLLSDEILEKFSLGTKPLGETQKPNSHLSLLSIVDSWHKL KINPYDHVICSTPLFRIWLGVTEYVFCTPGLLEQCIKHSITNQDFRPDDLEFVVAAR TWSKVVSYGSYKLYEQEFNDTQKYFAHMFPEATRIGNEMINTILSTT >Tyr1 (SEQ ID NO: 51) 4904-4134-6834, v.1 CELB-010-W01 -91- DSEIEIVQNGHYVSRKCDYILYCVEAENIGKIVSIYGPSTKVGSIVGGQTSCKAPE MAAFEAHLPSDVDIISCHSLHGPKVNPEGMPLVIIRHRNTEEWKFEFVQSLLESLK SKIVYLSAEQHDKITADTQAVTHAAFLTMGKAWQANGQYPWQISRWIGGLENAK MNISLRIYSNKWHVYAGLAISNPAAKVQIQQYASSAGDLYKLMITGKEQELLDRL TAARDFVFGGLKKEHSLLLSDEILEKFSLGTKPLGETQKPNSHLSLLSIVDSWHKL KINPYDHVICSTPLFRIWLGVTEYVFCTPGLLEQCIKHSITNQDFRPDDLEFVVAAR TWSKVVSYGSYKLYEQEFNDTQKYFAHMFPEATRIGNEMINTILSTT >DBR (SEQ ID NO: 52) MVNLSLRPRPAKAKFKGLPANLEVSPEDTVASVVAKLSAATKLSKSRIRLTVADEE NGGAPGAKKKHIVLKPEHAVGDYLFSDSPVVFVKDLGPQIPWRTVFILEYLGPLL AHPIIFFGQKFFYRQSFEYTFAQKLVFTLCMLHFLKREIETIYIHKFSSATMPLFNLF KNSGYYWFIAGFNLAFFVYAPASFSSPQAPLWKRFLFSTGFFERTPLFLNLMAAL WLWGETSNFWTHFNLASLRNDGSKDHKIPFGYGFNLVSCPNYFFEVVSWIAIAL MCGNWSAYVFTAIGFGQMYVWAVQKHRRYKREFGDRYPRNRKVMVPFLL >AtECR (SEQ ID NO: 53) MKVTVVSRSGREVLKAPLDLPDSATVADLQEAFHKRAKKFYPSRQRLTLPVTPGS KDKPVVLNSKKSLKEYCDGNNNSLTVVFKDLGAQVSYRTLFFFEYLGPLLIYPVF YYFPVYKFLGYGEDCVIHPVQTYAMYYWCFHYFKRILETFFVHRFSHATSPIGNV FRNCAYYWSFGAYIAYYVNHPLYTPVSDLQMKIGFGFGLVCQVANFYCHILLKNL RDPSGAGGYQIPRGFLFNIVTCANYTTEIYQWLGFNIATQTIAGYVFLAVAALIMT NWALGKHSRLRKIFDGKDGKPKYPRRWVILPPFL >MdECR (SEQ ID NO: 54) MKVTVVSRSGREVVKGGLELSDSATVADLQDAIHKRTKKFYPARQRLTLPVQPG SKERPVVLSYKKSLQDYISGNSDNLTVVFKDLGPQVSYRTLFFFEYLGPLILYPIFY YFPVYDYLGFKGDRVIHPVQTYALYYWCFHYFKRIMETFFVHRFSHATSPLSNVF RNCAYYWSFGAFIAYYLNHPLYTPVSDLQMKIGFGIGIICQISNFYCHXLLRNLRSP DGNGGYQIPRGFLFNIVTCANYTTEIYQWLGFNIATQTVAGYIFLIVAASIMTNWA LAKHRRLKKIFDGKDGRPKYPRRWVILPPFL >MAO3 (SEQ ID NO: 55) MTPHPFDQLSVPEMEKVVTVVKKAHNGKTLHLKSIGTEEPPKALMAPFLAAKRA GKNPTPPPRVAHCIFYVLQDKLVNQCWIDVTQGTVIKNEVIKKGIHPPIDPWEANE AFEAAFAHPLVKDAIKKCGLEHLIDNLTIDGWMYGCDSELEMPRFMQMLVYCRD PKTNHQDSNMYAFPVPFVPVYDVLEKKLVRVDFCATGGDDDDAAVKGVGNYDT RTEGKNCIEHCVANDYLPELQDKMRTDLKPYNVIQPDGPSYNIDKDGYVNWQK WQFKVGFTPREGLVIHDVHYDGRSTFYRLSMSEMAVPYADPRPPLHRKMAFDFG DCGGGKCANELTLGCDCLGTIKYFDGNVCDPEGNVFTRKNVICMHEQDDGIGW 4904-4134-6834, v.1 CELB-010-W01 -92- DAGKKSKFGNIVSPGVLAASHQHIFNMRMDPAIDGHKNTIYVNDTVSLPWDEKN PHGIAFENTKTPIEKSCYLDSDIQKNRYLKICNENKINPISGNPVGYKVGGLATAM LYAQPGSIARSRAAFATHHYWVTKYKDQEFFAGGVWTNQSANEIGGVQDAVARN ENVRNDDVVLWHSFGLTHHPRVEDFPVMPCEIMKVHLSPNDFFTGNPSVDVPKS NQTFNRSVEVKDCRSCKM >OMT1 (SEQ ID NO: 56) MSTTYKEYDWEKPVQLLYDHINGLPAEELAKFKKDPEALLDAIDKFEEEQHKKD GKYALMTVGPEKRKVVEEEIAQNKPYTFAELGGFCGYSAIAFAHKLKQTHPGYQ VHYYSLEVSPFFAKVTSRFTTLAGLGDIVTVLVGPAAEGLERLKEEYNHAKIDFFF IDHWKDLYVPDLQKAEELGLVQYGTVITADNIYWPGAPEYAKYVRLTPAEKKKE YPGKGNPNIEYDTRTVEVPLGKDKKDGVEVTLCTGVLTE >HAT1 (SEQ ID NO: 57) MDIATEWTTNANEALTITLEPSKGKGKGKEVSNGSEKSHVFNPIFTYPIYGDVETI LGYKNFELNLKMDASTMLPLVTVKFSDKLEFDGISFDDPVERLLEFLPEETATDEA EWEEKRVKELGDGFKPVGKEFGTFSVNSEKYTVHRSTLLDPETLKLHLRLQIFVP LFIEAGSYIDNEDDRWEIYIVYNAEKEIVGFSTVYCYWFYEPSAKESKAPKDASLE QLQKQPFSPTLRKRISQYVILPPFQGKGLGGQLYTLLFSRFYADPNVYEITVEDPSE AFDDLRDRCDLKWLADQGFPSEVFRMLQTTSAHGEKAGDNRTGRTKVVAGAF WTKWLEEHRLKYKLAHRQFARCFEMILLACLEVSSPTKKRNIKDARLFIKKRVY VRNREFLEELGGKIEVMSKLQETYESMEEDYARIMKPVLGYVKDGLKKRDRND AGNEEAKRVKVE >HBT1 (SEQ ID NO: 58) MTTTESIASDIEKGGITSHHENLDPVALTEELDPEHHKYLISRHGSVQLDPLPSADP EDPLNWPDWQKNYEILLIAFGTFSSTFMAAGLTPAFETMAEEYGVDLPTAAYFTS AQIAVFGVLPLFWVPLMNAYGRKPFLTVAALACCILNIGGGFAKTYGQQMATRVL VAVFVSAVTAAGSSVVGDLAFAHERGKKNGWWSLALLIGTPGGPFFTGFIQQHA GTKWIFFVFAIMNFIQFVLWIFARETIYTRASPEYYSQGLLKVVGIRKSSSRPFSWK MFFRPLKQAANLNITIAVIAASVTFCYANIVLVVEMPQVMVPLFHLDAQQMSLQY ISIIIGSIIGEVLAGPLSDWWMRRSTAKRNGQRVIADRLWVCYNGYILVIVGLLVW GIYLFKATPGHWSIKPLVGAAIAAAGNNIVATVVTTFAIDNAPHKAGDVGLYINFV RSLFGFLGPFYFPDMFENLNFAGSAGLMCGLVLLFAWVPTVVVHFIGARRAIKA >HBT2 (SEQ ID NO: 59) MTSSNTPSIDHEKGPMDDQVEKISTHGSHPASISEEHKQYLIAKHGTYELDPLPSM SDDDPLNWPDSFKFLQLGMVAFHGFMGTFMASGIVPSFGKYSEILDKPVPRVSYL TSAQIVLIGTFPMFWVPVMQRYGKRLLLIISVLGTMAFSIGAVFSTDYGTLMAMR CLSAVFVSPGLAVGGAIVKETTFSHQRGSRSGVWAISVNLGTMFGAFLMGFVAEY 4904-4134-6834, v.1 CELB-010-W01 -93- KITIFKFLEPLMFLLKPRVFIPAFGYTMMFMHGNIAMNVEIPQVMVHKFELGPQA LGLQFLSFVIGTVIGEVGGYLSDRLVQWGHKNNKGPSFRLWVTHPGYITCIVGLI VFGVQIQNIDHYNVTPLIGCAIAAFGLQIGTSPIIAYCIDSDHTKAVQISLFVTFLRQ LFAFIGPFYYPKMFDNLGFAEAYGIMAMLVGVLGWILTSCLQFWEQRHGR >YlMFP1 (SEQ ID NO: 60) MKVDSEVIPGTIQLVDLKGDPDYNAVDHEIVLVPTPSADPDDPLNWSQRRKWLS MLCMVLYTLGVGVPTASIFSVLLPISEKTNLSLADLNEGTGYMFLMLGFGCLFWQ PVALQFGKRPVYLISILGTMAVQIWAPYTKNNGQWIGHKILQGFLGAPIESLCEVT VSDIWFEHERGSWMGLYAFMMLFGSFMAPFFGGFITQGMDWKWVLFWGAIFDA VVFVFLFFFFEETNYSRKAELERECMESETLDVAHGGAVLPVGSGSFNDSSDQNE KGSANRVDVIPNPFSNGETAACGVPAKIYKPKTFWDKLKLFDKPRPNMLWTMVK RPIIILFSFPPVIYAGFLYGTGLIWFSVLNATASKILSEPPYNFKPSMVGVAYLCPTIIT AIVAWYGGWLGDRLRIWMAKRHGGISEAEDRLWLLALYMVMCPAGLILWGIGA AHGIHWFGLVMGLGITGGFGVLAGLCSVNYAVDCYREMASESMVPLIIIRNCMG FGMGYAITPWLTNEGLQRCFGEAAGVSVFCIGMFLFMIAFGKKFRIATRHRYWKF VQESIENDMAH >YlMFP2 (SEQ ID NO: 61) MSIHSSSSHDKDIVQIVEDSIGLSKTDTRSSHVSRASKASRAASDYQIDHIYGDMD RREITLARQITRETILSAYQEKVRSRASSIINGKIDPSTAPPPPLKNGGDGSQFLDVD PELVTWDGDEDPENPQNWHTYKKVATTVIVSLYTFVSPLTSSIISPAVPAIAAEYNE TRPVVQSLMVSIMILAWAICPLFVAPLSEMYGRKIVMDVSILVLLAFTLGCGGAQ NTAQMAVCRFFAGVGGAAPLSVGAGVLADLYSPQKRGTALAWYAIGPTVGPVVA PIAAGWIVQETNTWRWVMWVDGIFIGCVAACGFLFYSETYPPVLLQRKAKKLRK ESGNDALHTIYDIASEPLSSKLYTSMTRPLRILVTHPIVMGLGLFMAFTYGFMYIMI VTFPALWTERYGFSLGIMGLTFLGMGIGFLAGTWFWCVYTQKVYIKLRDQNGGV PKPEFRLPCIFAAPFLECIGLIWYGWSAESHVHWIMPIIGTGIFSFAVMDVFQTIQT YLIDMNPRFSASYVASASLFRSLFGFAMPLFGRQMYDAMGYGWANTMCGILAVV LGLPFPIIVWFYGERIRNRFDKKLEASQAKKDEKNMEKMRKRELERELKEQEKL DKEKNEHVHFVAVETSPSIKNEDSL >YlMFP3 (SEQ ID NO: 62) MFGSLGILQPRDYGGEVTGTVVMMGHRDKESKLMTRNDGDGVGEDADAANAT QGDSSDTTPSGVVTDPATVARAKASSESDSSDLKKTPGGIVLFPQPRNDPNDPLN WPIWRRDIALLVIGFHSFISGGQTPILASGFNIMAKEFDVTLNTLSYLVGAFMLAM AVGSAILAPTAVIYGKRMIYLISCLIFFGGAIWGGAAKSFGSLIGARIIMGIGASPTE SLPSSSIAEIYFMHERAYRLGIYTLLMLGGKNIVPLVSAFIISAKGWNWVFWVLAII VGMDFVLIFFFVPDTWFIRAPTPNKRSLEESMMAQEARANSLMSWNSRQSMRRD FLDEINVQEANEELREMEETAEKDAEKEAADKEAREDATNPTAPALTREVSFADE 4904-4134-6834, v.1 CELB-010-W01 -94- VEDQEEGDGDFPGFGPSTSAPGRPSYISRNLSYASHFSVASQDVPKKSYIQTLKPYI GRQSQDKLWMISLRPYVLYLYPPVMFSTLVYSMSVVWLIVVSETISHIFSSQPYNF PLTSVGLLYVSTFIGGCLGSAVAGKISDMFVRIMCRHNNGVYEPEFRLVMIVPVMI TTSMGLMGYGWATHDGDHWAVVCIFLGLLGFGCSLGSTTAITYCVDSYKMFASE ALVSLNVSKNVLGFVFSLFNTMAVESRGQKTVFLAYGGAQIFLCLFGIPLYIYGKR FRRWTDEMNLMKYLYVRTEDDADDADE >ACL1 (SEQ ID NO: 63) MSANENISRFDAPVGKEHPAYELFHNHTRSFVYGLQPRACQGMLDFDFICKRENP SVAGVIYPFGGQFVTKMYWGTKETLLPVYQQVEKAAAKHPEVDVVVNFASSRS VYSSTMELLEYPQFRTIAIIAEGVPERRAREILHKAQKKGVTIIGPATVGGIKPGCF KVGNTGGMMDNIVASKLYRPGSVAYVSKSGGMSNELNNIISHTTDGVYEGIAIGG DRYPGTTFIDHILRYEADPKCKIIVLLGEVGGVEEYRVIEAVKNGQIKKPIVAWAIG TCASMFKTEVQFGHAGSMANSDLETAKAKNAAMKSAGFYVPDTFEDMPEVLAE LYEKMVAKGELSRISEPEVPKIPIDYSWAQELGLIRKPAAFISTISDDRGQELLYAG MPISEVFKEDIGIGGVMSLLWFRRRLPDYASKFLEMVLMLTADHGPAVSGAMNTII TTRAGKDLISSLVAGLLTIGTRFGGALDGAATEFTTAYDKGLSPRQFVDTMRKQN KLIPGIGHRVKSRNNPDFRVELVKDFVKKNFPSTQLLDYALAVEEVTTSKKDNLIL NVDGAIAVSFVDLMRSCGAFTVEETEDYLKNGVLNGLFVLGRSIGLIAHHLDQK RLKTGLYRHPWDDITYLVGQEAIQKKRVEISAGDVSKAKTRS YlARO4_K221L (Y. lipolytica feed-back insensitive mutant) (SEQ ID NO: 64) MSRSSSPNASSAEDVRILGYDPLLAPALLQTEVASTKNARETVSKGRKDSIDVITG KSDKLLCIVGPCSLHDPKAAMEYAQRLKELSDKLSGELVIVMRAYLEKPRTTVG WKGLINDPDMDESFNINKGLRLSRKVFCDLTDLGLPIASEMLDTISPQFLADLLSL GAIGARTTESQLHRELASGLSFPVGFKNGTDGTLGVAVDAVQAASHPHHFMGVT LQGVAAITTTKGNENCFIILRGGKKGTNYDAESVAECKKATESMLMVDCSHGNS NKDYRNQPKVSKAVAEQVAAGEKKIIGVMIESNIHEGNQKVPKEGPSALKYGVS ITDACVSWETTVDMLTELANAVKERRNKN 4904-4134-6834, v.1

Claims

CLAIMS What is claimed is:

1. A recombinant host cell metabolically engineered to produce an increased yield of tyramine hydroxycinnamic acid amides from a substrate comprising at least one aldohexose, ketohexose, aldopentose, or glycerol, wherein the cell comprises: (a) nucleic acids which encode a tyrosine decarboxylase (TDC) enzyme (E.C. 4.1.1.25); (b) nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); (c) nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); and (d) nucleic acids which encode enzymes of the tyrosine biosynthesis pathway and tyrosine precursor metabolite biosynthesis pathways to enable production of sufficient quantities of tyrosine to support increased yield of tyramine hydroxycinnamic acid amide synthesis from the at least one aldohexose, ketohexose, or aldopentose substrate; (e) optionally, nucleic acids which encode a coumaroyltyramine-3-hydroxylase enzyme (CmT3H); (f) optionally, nucleic acids which encode an O-methyltransferase enzyme, capable of transferring a methyl group to the O3’ of caffeoyltyramine; wherein the TDC selectively decarboxylates tyrosine over phenylalanine and / or the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid, wherein the increased yield of tyramine hydroxycinnamic acid amides is compared to a yield of tyramine hydroxycinnamic acid amides obtained from a host cell which does not comprise either (b) or (c).

2. The recombinant host cell of claim 1, wherein the at least one aldohexose, ketohexose, or aldopentose substrate is selected from the group consisting of glucose, mannose, galactose, fructose, D-xylose, and L-arabinose.

3. The recombinant host cell of claim 2, wherein the aldohexose is glucose. {M0540533.1 }CELB-010-W01 -96- 4. The recombinant host cell of claim 1, the increased yield of tyramine hydroxycinnamic acid amides is a yield of at least 1 g / L.

5. The recombinant host cell of claim 1, wherein the recombinant host cell further comprises: (g) nucleic acids which encode enzymes of the phenylalanine biosynthesis pathway and phenylalanine precursor biosynthesis pathways to enable production of sufficient quantities of phenylalanine to support increased yield of hydroxycinnamic tyramine amide synthesis from at least one aldohexose, ketohexose, or aldopentose substrate; (h) nucleic acids which encode a phenylalanine ammonia lyase enzyme (PAL) (E.C. 4.3.1.24, 4.3.1.25), and nucleic acids which encode a cinnamate 4- monooxygenase enzyme (C4H) (E.C. 1.14.14.91); (i) optionally, nucleic acids which encode a 4-coumarate 3-hydroxylase enzyme (C3H), capable of adding a hydroxyl group to the C3’ of coumaric acid and / or coumaroyl-CoA and / or coumaroyl-tyramine; and (j) optionally, nucleic acids which encode an O-methyltransferase, capable of selectively transferring a methyl group to the O3’ of caffeic acid and / or caffeoyl-CoA rather than the O4’ of caffeic acid and / or caffeoyl-CoA.

6. The recombinant host cell of claim 1, wherein the TDC has an amino acid sequence with at least 65% identity to the amino acid sequence of TDC1 (SEQ ID NO: 1), TDC5 (SEQ ID NO: 2), TDC7 (SEQ ID NO: 3), TDC8 (SEQ ID NO: 4), or TDC9 (SEQ ID NO: 5), and wherein the TDC selectively decarboxylates tyrosine over phenylalanine.

7. The recombinant host cell of claim 6, wherein the TDC has an amino acid sequence with at least 85% identity to the amino acid sequence of TDC7 (SEQ ID NO: 3).

8. The recombinant host cell of claim 1, wherein the HCL has an amino acid sequence with at least 65% identity to the amino acid sequence of HCL1 (SEQ ID NO: 6), HCL2 (SEQ ID NO: 7), HCL3 (SEQ ID NO: 8), HCL7 (SEQ ID NO: 9), HCL8 (SEQ ID NO: 10), HCL9 (SEQ ID NO: 11), HCL11 (SEQ ID NO: 12), HCL12 (SEQ ID NO: 13), HCL13 (SEQ ID NO: 14), HCL14 (SEQ ID NO: 15), HCL15 4904-4134-6834, v.1CELB-010-W01 -97- (SEQ ID NO: 16), HCL16 (SEQ ID , HCL17 (SEQ ID NO: 18) or HCL18 (SEQ ID NO: 19).

9. The recombinant host cell of claim 8, wherein the HCL has an amino acid sequence with at least 85% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19), and wherein the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid.

10. The recombinant host cell of claim 1, wherein the THT has an amino acid sequence with 65% identity to the amino acid sequence of THT1 (SEQ ID NO: 20), THT2 (SEQ ID NO: 21), THT3 (SEQ ID NO: 22), THT17 (SEQ ID NO: 23), THT18 (SEQ ID NO: 24), THT19 (SEQ ID NO: 25), THT20 (SEQ ID NO: 26), THT22 (SEQ ID NO: 27), THT23 (SEQ ID NO: 28), THT24 (SEQ ID NO: 29), THT25 (SEQ ID NO: 30), THT26 (SEQ ID NO: 31), THT27 (SEQ ID NO: 32), THT31 (SEQ ID NO: 33), or THT32 (SEQ ID NO: 34).

11. The recombinant host cell of claim 1, wherein the CmT3H is present and comprises an amino acid sequence with at least 65% identity to the amino acid sequence of SEQ ID NO:

35.

12. The recombinant host cell of claim 11, wherein the recombinant host cell further comprises nucleic acids which encode one or more NADPH-cytochrome P450 reductases (CPR).

13. The recombinant host cell of claim 12, wherein the one or more CPRs comprise an amino acid sequence with at least 65% identity to the amino acid sequence of AtATR2 (SEQ ID NO: 36), AmCPR1 (SEQ ID NO: 37), and AmCPR2 (SEQ ID NO: 38).

14. The recombinant host cell of claim 1, wherein the CmT3H is present and comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared to caffeoyltyramine yields obtained in a recombinant host cell expressing the polypeptide of SEQ ID NO:

35. 4904-4134-6834, v.1CELB-010-W01 -98- 15. The recombinant host cell of claim 14, the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO:

35.

16. The recombinant host cell of claim 15, wherein the at least one amino acid modification comprises at least two and up to twenty amino acid modifications.

17. The recombinant host cell of claim 1, wherein at least one O-methyltransferase is present and comprises an amino acid sequence with at least 65% identity to the amino acid sequence of OMT6 (SEQ ID NO: 39), OMT7 (SEQ ID NO: 40), OMT8 (SEQ ID NO: 41), OMT9 (SEQ ID NO: 42), or OMT10 (SEQ ID NO: 43), wherein the at least one O-methyltransferase is capable of selectively transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine, rather than the O4’ of caffeic acid, caffeoyl-CoA and / or caffeoyltyramine.

18. The recombinant host cell of claim 5, wherein the PAL comprises an amino acid sequence with at least 65% identity to the amino acid sequence of AML1 (SEQ ID NO: 44).

19. The recombinant host cell of claim 5, wherein the C4H comprises an amino acid sequence with at least 65% identity to the amino acid sequence of SEQ ID NO:

45.

20. The recombinant host cell of claim 9, wherein the HCL comprises a first domain comprising the amino acid sequence TAXGL, wherein X signifies any amino acid.

21. The recombinant host cell of claim 9, wherein the HCL comprises a second domain comprising the amino acid sequence IQSDPITSXIK, wherein X signifies any amino acid.

22. The recombinant host cell of claim 1, wherein the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolites through at least one aromatic amino acid precursor metabolite biosynthesis pathway 4904-4134-6834, v.1CELB-010-W01 -99- and / or wherein the cell has been to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways, wherein the greater flux of at least one aromatic amino acid precursor metabolite, tyrosine and / or phenylalanine is compared to the flux of at least one aromatic amino acid precursor metabolite, tyrosine and / or phenylalanine in a control cell not engineered to provide the greater flux.

23. The recombinant host cell of claim 22, wherein the increased flux through an aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway.

24. The recombinant host cell of claim 22, wherein the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D-erythrose-4-phosphate, and chorismate.

25. The recombinant host cell of claim 23, wherein the aromatic amino acid precursor metabolite pathway enzyme is an enzyme of the pentose phosphate pathway, the glycolysis pathway, or the shikimate pathway.

26. The recombinant host cell of claim 1, wherein the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 65% identity to YlAro4 (SEQ ID NO: 46).

27. The recombinant host cell of claim 1, wherein the recombinant host cell expresses a feedback resistant ARO4 enzyme.

28. The recombinant host cell of claim 27, wherein the feedback resistant ARO4 enzyme comprises a substitution comprising K221L.

29. The recombinant host cell of claim 22, wherein the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is selected from ARO1, chorismite synthase, chorismite mutase, prephenate dehydrogenase, and hydroxyphenylpyruvate aminotransferase. 4904-4134-6834, v.1CELB-010-W01 -100- 30. The recombinant host cell of claim 29, the Aro1 enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47).

31. The recombinant host cell of claim 29, wherein the chorismite synthase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of ChS (SEQ ID NO: 48).

32. The recombinant host cell of claim 29, wherein the chorismite mutase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of ChM (SEQ ID NO: 49).

33. The recombinant host cell of claim 29, wherein the prephenate dehydrogenase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51).

34. The recombinant host cell of claim 1, wherein the recombinant host cell is a fungal cell, an algal or protist cell, a plant cell, or a bacterial cell.

35. The recombinant host cell of claim 34, wherein the fungal cell is a yeast cell selected from the group consisting of Yarrowia, Saccharomyces, Candida, Ashbya, Cyberlindnea, Kluveromyces, Arxula, Xanthophyllomyces, Schizosaccharomyces, Hansenula, Xanthophyllomyces, and Pichia.

36. The recombinant host cell of claim 35, wherein the yeast cell is Yarrowia.

37. The recombinant host cell of claim 34, wherein the fungal cell is selected from the group consisting of Mucor, Mortierella, Fusarium, Sarochladium, Trichosporon and Aspergillus.

38. The recombinant host cell of claim 34, wherein the algal or protist cell is selected from the group consisting of Thraustochytrium, Schizochytrium, Aurantiochytrium, Chlorella, Auxenochlorella, Nannochloropsis, Scenedesmus, Tetraselmis, Botryococcus, and Chlamydomonas.

39. The recombinant host cell of claim 34, wherein the plant cell is selected from the group consisting of Arabidopsis, Artemisia, Bambusoideae, Catharanthus, Glycine, Medicago, Nicotiana, Oryza, Oryzoideae, Phyllostachys, Physcomitrella, Pooideae, Silybum, Solanum, Taxus, or Vitis vinifera. 4904-4134-6834, v.1CELB-010-W01 -101- 40. The recombinant host cell of claim the bacterial cell is selected from the group consisting of Rhodococcus and Gordonia.

41. The recombinant host cell of claim 1, wherein the recombinant host cell has been engineered to inactivate or reduce expression of genes which encode at least one enzyme that catalyzes production of byproducts which reduce the yield of coumaroyltyramine, caffeoyltyramine, and / or feruloyltyramine.

42. The recombinant host cell of claim 41, wherein the recombinant host cell is engineered to inactivate or reduce expression of a native double bond reductase which acts on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl- CoA derivatives thereof, and the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof.

43. The recombinant host cell of claim 42, wherein the double bond reductase which is inactivated is DBR (SEQ ID NO: 52) or homologs thereof that act on cinnamoyl- CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof.

44. The recombinant host cell of claim 42, wherein the nucleic acids encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 80% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54).

45. The recombinant host cell of claim 41, wherein the recombinant host cell has been engineered to inactivate or reduce expression of polypeptide with tyramine monoamine oxidase activity.

46. The recombinant host cell of claim 45, wherein the polypeptide with tyramine monoamine oxidase activity is MAO3 (SEQ ID NO 55), or a homolog thereof.

47. The recombinant host cell of claim 41, wherein the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with O4’- methyltransferase activity. 4904-4134-6834, v.1CELB-010-W01 -102- 48. The recombinant host cell of claim 47, the polypeptide with O4’- methyltransferase activity is OMT1 (SEQ ID NO: 56), or homologs thereof that have O4’-methyltrasnferase activity.

49. The recombinant host cell of claim 41, wherein the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with tyramine acetylase activity.

50. The recombinant host cell of claim 49, wherein the polypeptide with tyramine acetylase activity is classified in E.C. 2.3.1.87 or contains the IPR000182 motif, and possesses tyramine acetylase activity.

51. The recombinant host cell of claim 50, wherein the polypeptide with tyramine acetylase activity is HAT1 (SEQ ID NO: 57), or homologs thereof which possess tyramine acetylase activity.

52. The recombinant host cell of claim 41, wherein the recombinant host cell has been engineered to inactivate or disrupt expression of a polypeptide with ATP-citrate lyase activity.

53. The recombinant host cell of claim 52, wherein the polypeptide with ATP-citrate lyase activity is ACL1 (SEQ ID NO: 63), or homologs thereof that possess ATP- citrate lyase activity.

54. The recombinant host cell of claim 1, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid or ferulic acid from a culture medium.

55. The recombinant host cell of claim 54, wherein the one or more transporters comprise polypeptides with an amino acid sequence with at least 65% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62).

56. A cell culture, comprising recombinant host cells according to claim 1, the cell culture further comprising: 4904-4134-6834, v.1CELB-010-W01 -103- (a) a nutrient medium comprising an ketohexose, aldopentose, or glycerol substrate, wherein the nutrient medium further comprises a buffer, a nitrogen source, amino acids, a pH adjuster, vitamins, minerals, and / or a cell extract; and (b) tyramine hydroxycinnamic acid amides produced by the recombinant host cells, wherein the tyramine hydroxycinnamic acid amides are present in an amount of at least 3 g / L.

57. The cell culture of claim 56, wherein the aldohexose substrate is glucose.

58. The cell culture of claim 57, wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 5 g / L, wherein the cell culture does not comprise exogenous coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid, and wherein the tyramine hydroxycinnamic acid amides were produced by the recombinant host cells without addition of supplemental coumaroyltyramine, caffeic acid, caffeoyltyramine, or ferulic acid.

59. The cell culture of claim 56, wherein the nutrient medium further comprises one or more of coumaric acid, coumaroyltyramine, caffeic acid, caffeoyltyramine, and ferulic acid.

60. The cell culture of claim 59, wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell are present in an amount of at least 10 g / L.

61. The cell culture of claim 60, wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise feruloyltyramine in at least 15 g / L.

62. The cell culture of claim 60, wherein the tyramine hydroxycinnamic acid amides produced by the recombinant host cell comprise caffeoyltyramine in at least 12 g / L 63. The cell culture of claim 60, wherein the cell culture comprises caffeic acid or ferulic acid, and wherein a portion of the caffeic acid or ferulic acid present is exogenous, not having been produced by the recombinant host cell.

64. The cell culture of claim 59, wherein recombinant host cell comprises nucleic acids which encode a transporter protein that increases uptake of coumaric acid, caffeic acid or ferulic acid, from a culture medium, and wherein the tyramine 4904-4134-6834, v.1CELB-010-W01 -104- hydroxycinnamic acid amides the recombinant host cell are present in an amount of at least 10 g / L.

65. The cell culture of claim 56, wherein the tyramine hydroxycinnamic acid amides were produced by the recombinant host cell in a week or less, five days or less, or three days or less.

66. A method of producing tyramine hydroxycinnamic acid amides comprising: culturing a recombinant host cell in the presence of an aldohexose, ketohexose, or aldopentose substrate for a period of time, wherein the recombinant host cell is metabolically engineered to produce an increased yield of tyramine hydroxycinnamic acid amides from at least one aldohexose, ketohexose, or aldopentose substrate, wherein the recombinant host cell comprises: (a) nucleic acids which encode a tyrosine decarboxylase (TDC) enzyme (E.C. 4.1.1.25); (b) nucleic acids which encode a hydroxycinnamoyl / 4-coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); (c) nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); and (d) nucleic acids which encode enzymes of the tyrosine biosynthesis pathway and tyrosine precursor biosynthesis pathways to enable production of sufficient quantities of tyrosine to support increased yield of tyramine and tyramine hydroxycinnamic acid amide synthesis from the at least one aldohexose, ketohexose, or aldopentose substrate; (e) optionally, nucleic acids which encode a coumaroyltyramine-3-hydroxylase enzyme (CmT3H); (f) optionally, nucleic acids which encode an O-methyltransferase enzyme, capable of transferring a methyl group to the O3’ of caffeoyltyramine; wherein the TDC selectively decarboxylates tyrosine over phenylalanine and / or the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid; thereby producing tyramine hydroxycinnamic acid amides. 4904-4134-6834, v.1CELB-010-W01 -105- 67. The method of claim 66, wherein the one aldohexose, ketohexose, or aldopentose substrate is selected from the group consisting of glucose, mannose, galactose, fructose, D-xylose, glycerol and L-arabinose.

68. The method of claim 67, wherein the aldohexose is glucose.

69. The method of claim 66, wherein the recombinant host cell is cultured in the presence of one or more of coumaric acid, caffeic acid or ferulic acid.

70. The method of claim 66, wherein the recombinant host cell is cultured in the presence of glucose and one or both of caffeic acid and ferulic acid.

71. The method of claim 66, further comprises isolating the tyramine hydroxycinnamic acid amides produced by the recombinant host cell.

72. The method of claim 66, wherein the recombinant host cell further comprises: (g) nucleic acids which encode enzymes of the phenylalanine biosynthesis pathway and phenylalanine precursor biosynthesis pathways to enable production of sufficient quantities of phenylalanine to support increased yield of hydroxycinnamic tyramine amide synthesis from at least one aldohexose, ketohexose, or aldopentose substrate; and (h) nucleic acids which encode a phenylalanine ammonia lyase enzyme (PAL) (E.C. 4.3.1.24, 4.3.1.25) and nucleic acids which encode a cinnamate 4- monooxygenase enzyme (C4H) (E.C. 1.14.14.91); (i) optionally, nucleic acids which encode a 4-coumarate 3-hydroxylase (C3H), capable of adding a hydroxyl group to the C3’ of coumaric acid, coumaroyl- CoA, and / or coumaroyltyramine; (j) optionally, nucleic acids which encode an O-methyltransferase , capable of transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine.

73. The method of claim 66, wherein the TDC has an amino acid sequence with at least 65% identity to the amino acid sequence of TDC1 (SEQ ID NO: 1), TDC5 (SEQ ID NO: 2), TDC7 (SEQ ID NO: 3), TDC8 (SEQ ID NO: 4), or TDC9 (SEQ ID NO: 5), and wherein the TDC selectively decarboxylates tyrosine over phenylalanine. 4904-4134-6834, v.1CELB-010-W01 -106- 74. The method of claim 73, wherein the an amino acid sequence with at least 80% identity to the amino acid sequence of TDC7 (SEQ ID NO: 3).

75. The method of claim 66, wherein the HCL has an amino acid sequence with at least 65% identity to the amino acid sequence of sequence of HCL1 (SEQ ID NO: 6), HCL2 (SEQ ID NO: 7), HCL3 (SEQ ID NO: 8), HCL7 (SEQ ID NO: 9), HCL8 (SEQ ID NO: 10), HCL9 (SEQ ID NO: 11), HCL11 (SEQ ID NO: 12), HCL12 (SEQ ID NO: 13), HCL13 (SEQ ID NO: 14), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), and HCL18 (SEQ ID NO: 19).

76. The method of claim 69, wherein the HCL has an amino acid sequence with at least 90% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19), and wherein the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid.

77. The method of claim 66, wherein the THT has an amino acid sequence with 65% identity to the amino acid sequence of THT1 (SEQ ID NO: 20), THT2 (SEQ ID NO: 21), THT3 (SEQ ID NO: 22), THT17 (SEQ ID NO: 23), THT18 (SEQ ID NO: 24), THT19 (SEQ ID NO: 25), THT20 (SEQ ID NO: 26), THT22 (SEQ ID NO: 27), THT23 (SEQ ID NO: 28), THT24 (SEQ ID NO: 29), THT25 (SEQ ID NO: 30), THT26 (SEQ ID NO: 31), THT27 (SEQ ID NO: 32), THT31 (SEQ ID NO: 33), or THT32 (SEQ ID NO: 34).

78. The method of claim 66, wherein the CmT3H is present and comprises an amino acid sequence with at least 80% to the amino acid sequence of SEQ ID NO:

35.

79. The method of claim 72, wherein the recombinant host cell further comprises nucleic acids which encode one or more NADPH-cytochrome P450 reductases (CPR).

80. The method of claim 79, wherein the one or more CPRs comprise an amino acid sequence with at least 65% identity to the amino acid sequence of AtATR2 (SEQ ID NO: 36), AmCPR1 (SEQ ID NO: 37), and AmCPR2 (SEQ ID NO: 38). 4904-4134-6834, v.1CELB-010-W01 -107- 81. The method of claim 66, wherein the is present and comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared with caffeoyltyramine yields obtained in a recombinant host cell expressing SEQ ID NO:

35.

82. The method of claim 81, wherein the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO:

35.

83. The method of claim 81, wherein the at least one amino acid modification comprises at least two and up to twenty amino acid modifications.

84. The method of claim 66, wherein at least one O-methyltransferase is present and comprises an amino acid sequence with at least 65% identity to the amino acid sequence of OMT6 (SEQ ID NO: 39), OMT7 (SEQ ID NO: 40), OMT8 (SEQ ID NO: 41), OMT9 (SEQ ID NO: 42), or OMT10 (SEQ ID NO: 43), wherein the at least one O-methyltransferase is capable of transferring a methyl group to the O3’ of caffeic acid, caffeoyl-CoA, and / or caffeoyltyramine.

85. The method of claim 84, wherein the at least one O-methyltransferase provides enhanced yield of feruloyltyramine and comprises an amino acid sequence with at least 80% identity to the amino acid sequence of OMT9 (SEQ ID NO: 42).

86. The method of claim 72, wherein the PAL comprises an amino acid sequence with at least 80% identity to the amino acid sequence of AML1 (SEQ ID NO: 44).

87. The method of claim 72, wherein the C4H comprises an amino acid sequence with at least 80% identity to the amino acid sequence of SEQ ID NO:

45.

88. The method of claim 66, wherein the HCL comprises a first domain comprising the amino acid sequence TAXGL, wherein X signifies any amino acid. 4904-4134-6834, v.1CELB-010-W01 -108- 89. The method of claim 66, wherein the a second domain comprising the amino acid sequence IQSDPITSXIK, wherein X signifies any amino acid.

90. The method of claim 66, wherein the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolites through at least one aromatic amino acid precursor biosynthesis pathway and / or wherein the cell has been engineered to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways.

91. The method of claim 90, wherein the increased flux through an aromatic amino acid precursor pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway.

92. The method of claim 90, wherein the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D- erythrose-4-phosphate, and chorismate.

93. The method of claim 90, wherein the aromatic amino acid precursor pathway enzyme is an enzyme of the pentose phosphate pathway, the glycolysis pathway, and the shikimate pathway.

94. The method of claim 66, wherein the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 80% identity to YlAro4 (SEQ ID NO: 46).

95. The method of claim 66, wherein the recombinant host cell expresses a feedback resistant ARO4 enzyme.

96. The method of claim 95, wherein the feedback resistant ARO4 enzyme comprises a substitution comprising K221L.

97. The method of claim 90, wherein the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is selected from ARO1, chorismite synthase, chorismite mutase, prephenate dehydrogenase, and hydroxyphenylpyruvate aminotransferase. 4904-4134-6834, v.1CELB-010-W01 -109- 98. The method of claim 97, wherein the comprises an amino acid sequence with at least 80% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47).

99. The method of claim 97, wherein the chorismite synthase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of ChS (SEQ ID NO: 48).

100. The method of claim 97, wherein the chorismite mutase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of ChM (SEQ ID NO: 49).

101. The method of claim 97, wherein the prephenate dehydrogenase enzyme comprises an amino acid sequence with at least 80% identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51).

102. The method of claim 66, wherein the recombinant host cell is a fungal cell, an algal cell or protist cell, a plant cell, or a bacterial cell.

103. The method of claim 102, wherein the fungal cell is Yarrowia, Saccharomyces, Candida, Ashbya, Cyberlindnea, Kluveromyces, Arxula, Xanthophyllomyces, Schizosaccharomyces, Hansenula, Xanthophyllomyces, or Pichia.

104. The method of claim 103, wherein the fungal cell is Yarrowia.

105. The method of claim 66, wherein the recombinant host cell has been engineered to inactivate or disrupt expression of genes which encode at least one enzyme that catalyzes production of byproducts which reduce the yield of coumaroyltyramine, caffeoyltyramine, and / or feruloyltyramine.

106. The method of claim 105, wherein the recombinant host cell is engineered to inactivate or reduce expression of a native double bond reductase which acts on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA derivatives thereof, and the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof. 4904-4134-6834, v.1CELB-010-W01 -110- 107. The method of claim 106, wherein bond reductase which is inactivated is DBR (SEQ ID NO: 52), or homologs thereof that act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-COA derivatives thereof.

108. The method of claim 106, wherein the nucleic acids encode an exogenous enoyl- CoA reductase enzyme with an amino acid sequence with 95% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54).

109. The method of claim 105, wherein the recombinant host cell has been engineered to inactivate or reduce expression of polypeptide with tyramine monoamine oxidase activity.

110. The method of claim 109, wherein the polypeptide with tyramine monoamine oxidase activity is MAO3 (SEQ ID NO: 55), or a homolog thereof.

111. The method of claim 105, wherein the recombinant host cells has been engineered to inactivate or disrupt expression of a polypeptide with O4’-methyltransferase activity.

112. The method of claim 111, wherein the polypeptide with O4’-methyltransferase activity is OMT1 (SEQ ID NO: 56), or homologs thereof that have O4’- methyltrasnferase activity.

113. The method of claim 105, wherein the recombinant host cell has been engineered to inactivate or reduce expression of a polypeptide with tyramine acetylase activity.

114. The method of claim 113, wherein the polypeptide with tyramine acetylase activity is classified in E.C. 2.3.1.87 or contains the IPR000182 motif, and possess tyramine acetylase activity.

115. The method of claim 113, wherein the polypeptide with tyramine acetylase activity is HAT1 (SEQ ID NO: 57), or homologs thereof which possess tyramine acetylase activity.

116. The method of claim 105, wherein the recombinant host cells has been engineered to inactivate or disrupt expression of a polypeptide with ATP-citrate lyase activity. 4904-4134-6834, v.1CELB-010-W01 -111- 117. The method of claim 116, wherein with ATP-citrate lyase activity is ACL1 (SEQ ID NO: 63) , or homologs thereof that possess ATP-citrate lyase activity.

118. The method of claim 66, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid, ferulic acid, coumaroyltyramine and / or caffeoyltyramine from a culture medium.

119. The method of claim 118, wherein the one or more transporters comprise polypeptides with an amino acid sequence with at least 85% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62).

120. A polypeptide with coumaroyltyramine 3-hydroxylase activity, wherein the polypeptide comprises at least one amino acid modification compared to the amino acid sequence of SEQ ID NO: 35, wherein the at least one amino acid modification provides an improved yield of caffeoyltyramine compared with caffeoyltyramine yields obtained in a recombinant host cell expressing a polypeptide with an amino acid sequence of SEQ ID NO:

35.

121. The polypeptide with coumaroyltyramine 3-hydroxylase activity of claim 120, wherein the at least one amino acid modification comprises at least one deletion, substitution, or insertion at an amino acid position selected from R48, F52, I67, R95, H96, T98, S100, A101, F104, D110, I112, W113, Y120, R124, T128, L129, S133, K135, V208, T210, G211, N212, S219, E222, H223, H241, D294, Q297, A298, T302, T363, L365, M366, L367, M420, Q423, L428, F430, R434, R435, I436, T441, T444, Y445, L476, V477, and A478 of the amino acid sequence of SEQ ID NO:

35.

122. The polypeptide with coumaroyltyramine 3-hydroxylase activity of claim 121, wherein the at least one amino acid modification comprises at least two and up to twenty amino acid modifications.

123. A recombinant host cell engineered to produce (a) an enhanced titer of at least one of caffeic acid, ferulic acid, and / or a compound derived therefrom compared to a control cell by disruption or deletion of an endogenous gene coding for a 4904-4134-6834, v.1CELB-010-W01 -112- polypeptide capable of methylating to produce isoferulic acid, and / or (b) an enhanced titer of at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl- CoA and feruloyl-CoA compared to a control cell by disrupting or deleting an endogenous polypeptide which is capable of reducing at least one of cinnamoyl- CoA, coumaroyl-CoA, caffeoyl-CoA and feruloyl-CoA, wherein the control cell of (a) is a cell which expresses the endogenous polypeptide which is capable of methylating caffeic acid to produce isoferulic acid and the control cell of (b) is a cell which expresses the endogenous polypeptide capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA and feruloyl-CoA.

124. The recombinant host cell of claim 123, wherein the endogenous gene which has been disrupted or deleted comprises a nucleic acid sequence which encodes a polypeptide with 85% identity to OMT1 (SEQ ID NO: 56), or homologs thereof which are capable of methylating caffeic acid to produce isoferulic acid.

125. The recombinant host cell of claim 123, wherein the endogenous gene encoding a polypeptide capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA comprises a nucleic acid which encodes an amino acid sequence with 85% identity to DBR (SEQ ID NO: 52), or homologs thereof which are capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruloyl-CoA.

126. The recombinant host cell of claim 123, wherein a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde is also disrupted or deleted in the recombinant host cell.

127. The recombinant host cell of claim 126, wherein the endogenous gene encoding a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde comprises a nucleic acid which encodes an amino acid sequence with 85% identity to MAO3 (SEQ ID NO: 55), or homologs thereof.

128. The recombinant host cell of claim 123, wherein the enhanced titer of ferulic acid, cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruoyl-CoA is achieved in 4904-4134-6834, v.1CELB-010-W01 -113- the presence of a glucose and / or without caffeic acid supplementation.

129. The recombinant host cell of claim 123, wherein the enhanced titer of ferulic acid, cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and / or feruoyl-CoA is achieved in the presence of a glucose and / or glycerol.

130. The recombinant host cell of claim 123, wherein the recombinant host cell further comprises nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12).

131. The recombinant host cell of claim 130, wherein the HCL has an amino acid sequence with at least 65% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9), HCL14 (SEQ ID NO: 15), HCL15 (SEQ ID NO: 16), HCL16 (SEQ ID NO: 17), HCL17 (SEQ ID NO: 18), or HCL18 (SEQ ID NO: 19), and wherein the HCL selectively ligates CoA to one or more of 4-Coumaric acid, Caffeic acid, and ferulic acid over cinnamic acid.

132. The recombinant host cell of claim 131, wherein the HCL comprise a first domain comprising the amino acid sequence TAXGL, and a second domain comprising the amino acid sequence IQSDPITSXIK, wherein X in both amino acid sequences signify any amino acid.

133. The recombinant host cell of claim 123, wherein the recombinant host cell further comprises nucleic acids which encode a cinnamate 4-monooxygenase enzyme (C4H) (E.C. 1.14.14.91).

134. The recombinant host cell of claim 133, wherein the C4H comprises an amino acid sequence with at least 85% identity to the amino acid sequence of SEQ ID NO:

45.

135. The recombinant host cell of claim 123, wherein the cell has been engineered to provide greater flux of at least one aromatic amino acid precursor metabolites through at least one aromatic amino acid precursor metabolite biosynthesis pathway and / or wherein the cell has been engineered to provide greater flux of tyrosine and / or phenylalanine through the respective tyrosine and phenylalanine biosynthesis pathways. 4904-4134-6834, v.1CELB-010-W01 -114- 136. The recombinant host cell of claim the increased flux through an aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway is accomplished by overexpressing at least one enzyme of the aromatic amino acid precursor metabolite pathway, tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway.

137. The recombinant host cell of claim 135, wherein the at least one aromatic amino acid precursor metabolite is selected from the group consisting of phosphoenolpyruvate, D-erythrose-4-phosphate, and chorismate.

138. The recombinant host cell of claim 135, wherein the aromatic amino acid precursor metabolite pathway enzyme is an enzyme of the pentose phosphate pathway, the glycolysis pathway, or the shikimate pathway.

139. The recombinant host cell of claim 123, wherein the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 90% identity to YlAro4 (SEQ ID NO: 46).

140. The recombinant host cell of claim 123, wherein the recombinant host cell expresses a feedback resistant ARO4 enzyme.

141. The recombinant host cell of claim 140, wherein the feedback resistant ARO4 enzyme comprises a substitution comprising K221L.

142. The recombinant host cell of claim 135, wherein the at least one enzyme of the tyrosine biosynthesis pathway or phenylalanine biosynthesis pathway which is overexpressed is selected from ARO1, chorismite synthase, chorismite mutase, prephenate dehydrogenase, and hydroxyphenylpyruvate aminotransferase.

143. The recombinant host cell of claim 142, wherein the Aro1 enzyme comprises an amino acid sequence with at least 85% identity to the amino acid sequence of YlAro1 (SEQ ID NO: 47).

144. The recombinant host cell of claim 142, wherein the chorismite synthase enzyme comprises an amino acid sequence with at least 85% identity to the amino acid sequence of ChS (SEQ ID NO: 48). 4904-4134-6834, v.1CELB-010-W01 -115- 145. The recombinant host cell of claim the chorismite mutase enzyme comprises an amino acid sequence with at least 85% identity to the amino acid sequence of ChM (SEQ ID NO: 49).

146. The recombinant host cell of claim 142, wherein the prephenate dehydrogenase enzyme comprises an amino acid sequence with at least 85% identity to the amino acid sequence of Tyr1 (SEQ ID NO: 51).

147. The recombinant host cell of claim 123, wherein the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme which does not act on cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA derivatives thereof.

148. The recombinant host cell of claim 147, wherein the nucleic acids encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 85% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54).

149. The recombinant host cell of claim 123, wherein the recombinant host cell is a fungal cell, an algal or protist cell, a plant cell, or a bacterial cell.

150. The recombinant host cell of claim 149, wherein the fungal cell is Yarrowia lipolytica.

151. A recombinant host cell metabolically engineered to produce at least 1 g / L of tyramine hydroxycinnamic acid amides from a substrate comprising at least one of aldohexose, ketohexose, aldopentose, or glycerol, wherein the cell comprises: (a) nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); and (b) nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); wherein an endogenous gene encoding a polypeptide capable of methylating caffeic acid to produce isoferulic acid is disrupted or deleted in the recombinant host cell.

152. The recombinant host cell of claim 151, wherein the endogenous gene which has been disrupted or deleted comprises a nucleic acid sequence which encodes a 4904-4134-6834, v.1CELB-010-W01 -116- polypeptide with 80% identity to ID NO: 56), or homologs thereof which are capable of methylating caffeic acid to produce isoferulic acid.

153. The recombinant host cell of claims 151, wherein the recombinant host cell is a fungal cell, an algal or protist cell, a plant cell, or a bacterial cell.

154. The recombinant host cell of claim 153, wherein the fungal cell is Yarrowia lipolytica.

155. The recombinant host cell of claim 151, wherein an endogenous gene encoding a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde is disrupted or deleted in the recombinant host cell.

156. The recombinant host cell of claim 155, wherein the endogenous gene encoding a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde comprises a nucleic acid which encodes an amino acid sequence with 95% identity to MAO3 (SEQ ID NO: 55), or homologs thereof.

157. The recombinant host cell of claim 151, wherein the recombinant host cell comprises nucleic acids which encode a polypeptide having an amino acid sequence with at least 65% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9) and is capable of selectively ligating CoA to 4-coumaric acid, caffeic acid and ferulic acid over cinnamic acid, and overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 80% identity to YlAro4 (SEQ ID NO: 46).

158. The recombinant host cell of claim 151, wherein an endogenous gene encoding a polypeptide with 80% identity to DBR (SEQ ID NO: 52), or homologs thereof which are capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA and feruloyol-CoA, is disrupted or deleted, wherein the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 80% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54).

159. The recombinant host cell of claim 151, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake 4904-4134-6834, v.1CELB-010-W01 -117- of caffeic acid, ferulic acid, and / or caffeoyltyramine from a culture medium.

160. The recombinant host cell of claim 159, wherein the one or more transporters comprise polypeptides with an amino acid sequence with at least 80% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62).

161. A recombinant host cell metabolically engineered to produce at least 1 g / L of tyramine hydroxycinnamic acid amides from a substrate comprising at least one aldohexose, ketohexose, aldopentose, or glycerol, wherein the cell comprises: (a) nucleic acids which encode a hydroxycinnamoyl / coumarate: Co-enzyme A (CoA) ligase enzyme (HCL) (E.C. 6.2.1.12); and (b) nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); wherein an endogenous gene encoding a polypeptide with 65% identity to DBR (SEQ ID NO: 52), or homologs thereof which are capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA and feruloyol-CoA, is disrupted or deleted in the recombinant host cell, and wherein the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 80% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54).

162. The recombinant host cell of claims 161, wherein the recombinant host cell is a fungal cell, an algal or protist cell, a plant cell, or a bacterial cell.

163. The recombinant host cell of claim 162, wherein the fungal cell is Yarrowia lipolytica.

164. The recombinant host cell of claim 161, wherein an endogenous gene encoding a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde is disrupted or deleted in the recombinant host cell. 4904-4134-6834, v.1CELB-010-W01 -118- 165. The recombinant host cell of claim the endogenous gene encoding a polypeptide capable of oxidizing tyramine to hydroxymethyl-acetaldehyde comprises a nucleic acid which encodes an amino acid sequence with 80% identity to MAO3 (SEQ ID NO: 55), or homologs thereof.

166. The recombinant host cell of claim 161, wherein the recombinant host cell comprises nucleic acids which encode a polypeptide having an amino acid sequence with at least 65% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9) and is capable of selectively ligating CoA to 4-coumaric acid, caffeic acid and ferulic acid over cinnamic acid, and overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 80% identity to YlAro4 (SEQ ID NO: 46).

167. The recombinant host cell of claim 161, wherein the recombinant host cell comprises nucleic acids which encode at least one transporter that increases uptake of caffeic acid, ferulic acid, coumaroyltyramine and / or caffeoyltyramine from a culture medium.

168. The recombinant host cell of claim 167, wherein the one or more transporters comprise polypeptides with an amino acid sequence with at least 80% identity to the amino acid sequence of HBT1 (SEQ ID NO: 58), HBT2 (SEQ ID NO: 59), YlMFP1 (SEQ ID NO: 60), YlMFP2 (SEQ ID NO: 61), or YLMFP3 (SEQ ID NO: 62).

169. A method of producing at least 1 g / L of tyramine hydroxycinnamic acid amides comprising: culturing the recombinant host cell of claim 151 in the presence of an aldohexose, ketohexose, aldopentose, or glycerol substrate for a period of time.

170. The method of claim 169, wherein the method further comprises culturing the recombinant host cell in the presence of at least one of tyramine, coumaric acid, caffeic acid, and ferulic acid.

171. A recombinant cell engineered to produce 1 g / L to 75 g / L of tyramine hydroxycinnamic acid amides within one week, wherein the recombinant cell comprises: (a) nucleic acids which encode a polypeptide having an amino acid sequence with at least 65% identity to the amino acid sequence of HCL7 (SEQ ID NO: 9) 4904-4134-6834, v.1CELB-010-W01 -119- and is capable of selectively to 4-coumaric acid, caffeic acid and ferulic acid over cinnamic acid; (b) nucleic acids which encode a tyramine-N-hydroxycinnamoyl-CoA transferase enzyme (THT) (E.C. 2.3.1.110); wherein endogenous genes encoding: (i) a polypeptide with 80% identity to DBR (SEQ ID NO: 52), or homologs thereof which are capable of reducing at least one of cinnamoyl-CoA, coumaroyl-CoA, caffeoyl-CoA and feruloyol- CoA, (ii) a polypeptide with 80% identity to OMT1 (SEQ ID NO: 56), or homologs thereof which are capable of methylating caffeic acid to produce isoferulic acid, and (iii) a polypeptide with 80% identify to MAO3 (SEQ ID NO: 55), or homologs thereof which are capable of oxidizing tyramine to hydroxymethyl-acetaldehyde, are disrupted or deleted in the recombinant host cell, wherein the recombinant host cell further comprises nucleic acids which encode an exogenous enoyl-CoA reductase enzyme with an amino acid sequence with 80% identity to the amino acid sequence of at least one of AtECR (SEQ ID NO: 53) and MdECR (SEQ ID NO: 54); and wherein the recombinant host cell overexpresses a wild type ARO4 enzyme comprising an amino acid sequence with 80% identity to YlAro4 (SEQ ID NO: 46).

172. A process for isolating caffeoyltyramine (CT) and / or feruloyltyramine (FT) produced from a recombinant host cell, the process comprising the steps of: 1) subjecting a fermentation broth containing the recombinant host cell along with the produced FT and / or CT to centrifugation to obtain a cell pellet; 2) adding alkaline water having a pH of 12.5-14 to the cell pellet to selectively redissolve the CT or FT, and removing solid cellular debris to obtain an alkaline solution comprising CT or FT; 3) acidifying the alkaline solution to a pH of 5 to 6.5 to precipitate CT or FT; and 4904-4134-6834, v.1CELB-010-W01 -120- 4) subjecting the precipitated CT or filtration to obtain isolated CT or FT.

173. The process of claim 172, further comprising the steps of: 5) redissolving the isolated CT or FT in ethanol; 6)filtering the ethanol solution to remove insoluble materials; 7) diluting the ethanol solution with 3-4 volumes of water to precipitate CT and FT; and 8) subjecting the precipitated CT or FT to filtration to obtain further isolated solid CT or FT. 4904-4134-6834, v.1

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