93 results about "Acetyl coenzyme" patented technology

The invention belongs to the field of biosynthesis, and in particular relates to LBD (Levandanenediol Pyrophosphate) synthase and engineered yeast for producing sclareol. In order to solve the problem that in the prior art, the sclareol biosynthesis yield is generally low, LSLPPs mutant containing at least one mutation of D730L, D374L, N674L or G379M is obtained by performing mutation and optimization on LSLPPs pyrophosphate synthase, and the mutant is used for sclareol synthesis. Meanwhile, in order to solve the problem of genetic instability caused by free plasmid expression of part of saccharomyces cerevisiae strains, a sclareol synthesis pathway is constructed in a yeast genome, and meanwhile, an acetyl coenzyme A synthesis pathway, an MVA pathway and a sclareol synthesis pathway are enhanced; chassis bacteria for synthesizing sclareol are modified in a manner of knocking out part of transcription inhibition factors, and the yield of a 5L fermentation tank reaches 26.11 g / L and is greatly improved compared with the prior art.

The invention belongs to the field of biosynthesis, and particularly relates to sclareol synthase and engineered yeast for producing sclareol. In order to solve the problem that in the prior art, sclareol biosynthesis yield is generally low, sclareol synthase is mutated and optimized, an SsScs mutant containing at least one mutation of Y491F, G307L or N269F is obtained, and the mutant is used for sclareol synthesis. Meanwhile, in order to solve the problem of genetic instability caused by free plasmid expression of part of saccharomyces cerevisiae strains, a sclareol synthesis pathway is constructed in a yeast genome, and meanwhile, an acetyl coenzyme A synthesis pathway, an MVA pathway and a sclareol synthesis pathway are enhanced; chassis bacteria for synthesizing sclareol are modified in a manner of knocking out part of transcription inhibition factors, and the yield of a 5L fermentation tank reaches 21.13 g / L and is greatly improved compared with the prior art.

The application provides a recombinant Yarrowia lipolytica capable of producing palmitoleic acid at a high yield, a construction method and application thereof, and belongs to the technical field of bioengineering. Yarrowia lipolytica The recombinant Yarrowia lipolytica is obtained by knocking out peroxisome biogenesis factor 10 and triacylglycerol lipase 4 in the genome of Yarrowia lipolytica and inserting an acetyl-CoA carboxylase, a Δ9 desaturase, an acetyl-CoA diacylglycerol acyltransferase, a glycerol-3-phosphate acyltransferase, a lysophosphatidylcholine acyltransferase and a phosphatidylcholine:diacylglycerol acyltransferase gene expression cassette. Experiment proves that the recombinant Yarrowia lipolytica can efficiently ferment and produce palmitoleic acid, and realizes efficient synthesis of the natural product palmitoleic acid from plants in Yarrowia lipolytica.

This invention relates to a recombinant Halomonas strain that produces polyhydroxyalkanoates (PHA) by overexpressing endogenous enzymes encoding ADP-dependent acetyl-CoA synthase (ADP-ACS). acd This gene not only enhances the recombinant bacterium's tolerance to acetic acid but also enables it to efficiently convert acetic acid or acetate substrates into acetyl-CoA, thereby participating in the tricarboxylic acid cycle (TCA cycle) and the synthesis of PHA. The present invention also relates to a method for producing PHA using the aforementioned recombinant Halomonas bacterium employing a pH-stat strategy.

The present disclosure describes a recombinant yeast host cell having a first engineered metabolic pathway to convert fructose-6-phosphate (F-6-P) into acetyl-coenzyme A. The first engineered metabolic pathway comprises: a genetic modification for expressing a heterologous phosphoketolase capable of converting fructose-6-phosphate into erythrose-4-phosphate, and at least one genetic modification for decreasing native 6- phosphofructo-2-kinase activity classified under Enzyme Commission No. 2.7.1.105. Optionally, the recombinant yeast host cell comprises a second engineered metabolic pathway for convert acetyl-coA into a fermentation product. The present disclosure further describes a process for making a fermentation product. The process comprises contacting the recombinant yeast host cell described herein with a carbohydrate source under a condition allowing the conversion of at least a part of the carbohydrate into a fermentation product.

The invention provides non-naturally occurring microbial organisms containing enzymatic pathways and / or metabolic modifications for enhancing carbon flux through acetyl-CoA. In some embodiments, the microbial organisms of the invention having such pathways also include pathways for generating reducing equivalents, formaldehyde fixation and / or formate assimilation. The enhanced carbon flux through acetyl-CoA, in combination with pathways for generating reducing equivalents, formaldehyde fixation and / or formate assimilation can, in some embodiments, be used for production of a bioderived compound. Accordingly, in some embodiments, the microbial organisms of the invention can include a pathway capable of producing a bioderived compound of the invention. The invention still further provides a bioderived compound produced by a microbial organism of the invention, culture medium having the bioderived compound of the invention, compositions having the bioderived compound of the invention, a biobased product comprising the bioderived compound of the invention, and a process for producing a bioderived compound of the invention.

The invention discloses a genetically engineered bacterium for synthesizing N-acetyl blue as well as a construction method and application of the genetically engineered bacterium. The genetically engineered bacterium is prepared by knocking out a lactic dehydrogenase gene ldh and inserting a phosphoketolase gene xfpK on a knockout site, knocking out a pyruvate oxidase gene poxB and inserting a phosphate transacetylase gene pta on a knockout site of a microorganism for producing N-acetyl blue, and knocking out an aconitase inhibition factor gene acnR, inserting a glutamate dehydrogenase gene gdhA on a knockout site, knocking out a glutamine synthetase adenylation transferase gene glnE, and inserting an alpha-ketoglutarate dehydrogenase inhibition factor gene odhI on a knockout site to obtain the strain. According to the method, the supply of the precursor acetyl coenzyme A is enhanced by introducing a non-oxidative glycolysis pathway, the pH dynamic regulation system balances the metabolic flux, and the double breakthrough of the yield and the carbon recovery rate of the N-acetyl blue is realized by combining a two-stage fermentation process.

The invention discloses a recombinant bacterium for producing mevalonic acid by taking glucose and acetone as co-substrates as well as a construction method and application of the recombinant bacterium, and belongs to the technical field of genetic engineering. The problems that an existing mevalonic acid biosynthesis mode is low in carbon atom economy, limited in theoretical yield and the like are solved. According to the invention, acetone carboxylase, acetoacetyl coenzyme A synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase and hydroxymethyl glutaryl-CoA synthetase are subjected to heterologous expression in escherichia coli with an acetyl coenzyme A acetyltransferase gene atoB and a histidine protein kinase gene atoS knocked out, and self carbonic anhydrase is over-expressed; and a new way for synthesizing MVA by using glucose and acetone as a co-substrate is constructed. According to the method, one molecule of CO2 can be fixed in the biosynthesis of mevalonic acid, the yield of carbon atoms in the synthesis process of mevalonic acid is increased, the problem of low yield of carbon atoms in the synthesis process of mevalonic acid by taking glucose as a single substrate is solved, and a new thought is provided for constructing a carbon neutralization type biological manufacturing technology.

The present application relates to a method for improving the conversion rate of ethanol to acetyl-CoA in yeast, an engineered bacterium and its application in the production of 3-hydroxypropionic acid. The engineered bacterium lacks pfk1 and pfk2 genes; the engineered bacterium also overexpresses mutACC1, MCRC, MCRN, Zwf1, Gnd1, Tal1, Rki1, Rpe1, Tkl1 and the fused CaGAPDH and Pos5 genes. The present application systematically combs and modifies the metabolic pathway of ethanol to acetyl-CoA in Saccharomyces cerevisiae, effectively improves the conversion rate of ethanol to acetyl-CoA, and through adaptive laboratory evolution, the intracellular reducing power and energy balance are remodeled, realizing the efficient and stable synthesis of 3-hydroxypropionic acid in Saccharomyces cerevisiae. In addition, the present application remolds the central metabolism of yeast, providing a new idea for efficient conversion of low-carbon compounds using synthetic biology methods.

The invention discloses a compound enzyme preparation-containing nutritional feed for regulating and controlling intramuscular fat of black pigs and a preparation method of the compound enzyme preparation-containing nutritional feed, and relates to the technical field of livestock and poultry breeding feeds. The invention discloses a black pig skeletal muscle cell fat directional transport feed which is prepared from the following components in parts by weight: 850-920 parts of basal feed, 5-12 parts of fat directional deposition compound enzyme group, 25-40 parts of amino acid-enzymatic synthesis substrate combination and 2-6 parts of lipolytic enzyme specific inhibitor. According to the black pig skeletal muscle cell fat directional transport feed, fat precursor directional transport is realized through the compounded fat directional deposition compound enzyme group, a fat synthesis pathway targeting black pig skeletal muscle cells and lipoprotein lipase; acetyl-coenzyme A carboxylase and fatty acid synthetase catalyze fat synthesis step by step, only intramuscular fat generation pathways are activated, subcutaneous and abdominal fat deposition paths are blocked, the technical defects that fat deposition of an existing single enzyme preparation is non-directional, and the body fat rate is caused to be abnormally increased are overcome, meanwhile, an exclusive amino acid-enzymatic synthesis substrate combination is matched, and the body fat synthesis efficiency is improved. Sufficient adaptive substrates are supplied to enzyme group catalytic reaction, and the problem that a single enzyme preparation is insufficient in catalytic efficiency is solved.

This invention relates to the field of biosynthesis technology, and particularly to engineered yeast strains and their application in the total fermentation production of steviol glycosides. This invention utilizes site-directed mutagenesis to mutate wild-type kaurenoic acid 13-hydroxylase, obtaining the G481L / Q159L mutant. This mutant is then applied to the production of steviol or steviol glycosides, constructing a steviol or steviol glycoside synthesis pathway in the *Saccharomyces cerevisiae* host to achieve efficient production of steviol or steviol glycosides. Simultaneously, by enhancing the level of diterpene precursor synthesis genes in chassis cells (MVA pathway, acetyl-CoA, GGPP, transport proteins, UDPG pathway), the yield of steviol glycosides is further increased, reducing costs for industrial production.

The invention relates to an acetyl coenzyme A probe as well as a preparation method and application thereof. Specifically, the acetyl coenzyme A optical probe comprises acetyl coenzyme A sensitive polypeptide and optical active polypeptide, and the optical active polypeptide is located in the sequence of the acetyl coenzyme A sensitive polypeptide.

A genetically engineered microbe capable of producing isoprene from glycerol includes at least a native nucleic acid sequence encoding at least a native enzyme capable of catalyzing one or more steps of a conversion from at least a carbon source to acetyl coenzyme A (A-CoA), at least a first heterologous nucleic acid sequence encoding at least a first enzyme of a mevalonate (MVA) pathway, and at least a second heterologous nucleic acid sequence encoding at least a second enzyme capable of catalyzing at least a terpene-producing chemical reaction, wherein the at least a carbon source includes glycerol.

The application discloses a Pichia pastoris engineering bacterium for converting methanol to synthesize bakuchiol from scratch as well as construction and application of the bacterium. In different chromosomal neutral sites of the Pichia pastoris, a heterologous p-coumaric acid synthesis pathway is introduced, key genes of tyrosine and phenylalanine synthesis pathways of a heterologous shikimic acid pathway are knocked out, overexpressed or heterologously expressed, a high-yield p-coumaric acid strain is obtained, on the basis of the strain, a heterologous bakuchiol biosynthesis pathway is introduced, bakuchiol synthetase is overexpressed, key genes of a MVA pathway and genes of an exogenous acetyl coenzyme A supply pathway are endogenously overexpressed or heterologously expressed, after optimization of a methanol concentration and back complementation of a His4 gene of the strain, the yield of the bakuchiol is effectively increased to 91.2 mg / L, which is 59.8 times higher than that of an initial strain, and the yield of the bakuchiol in a 15L fermenter reaches 692.8 mg / L. The application has the characteristics of high conversion efficiency, low production cost, easy preparation, wide industrial application prospect and the like.

The invention relates to the technical field of bioengineering, in particular to a recombinant halophilic bacterium for producing PHBV by using acetate as a single carbon source and application of the recombinant halophilic bacterium. The expression and / or activity of 2-methyl citrate synthetase and succinate dehydrogenase assembly factor 2 of the recombinant halophilic bacteria provided by the invention are reduced, 3-hydroxyvaleric acid synthetic genes scpA and scpB are overexpressed, an ADP-dependent acetyl coenzyme A synthetase gene acd is overexpressed, and a heterologous monocarboxylic acid transporter gene mctC is expressed. The strain can generate PHBV without adding precursors such as propionic acid and valeric acid, acetic acid or acetate can be used as a sole carbon source to produce PHBV, the yield is close to that when glucose is used as a carbon source, and the problems that the added precursor substances have certain toxicity, so that the growth of thalli is influenced, and the yield is reduced are solved; environmental pollution caused by addition of precursor substances is avoided, and meanwhile, the fermentation production cost of the PHBV is effectively reduced.

The present application relates to the technical field of genetic engineering, and discloses a recombinant Escherichia coli for high-yield O-acetyl-L-homoserine and application thereof. The recombinant Escherichia coli for high-yield O-acetyl-L-homoserine is obtained by the following combination of modification strategies: in Escherichia coli W3110, a gene encoding homoserine O-acetyltransferase is integrated into a gene site encoding L-arginine ABC transporter ATP binding subunit, then a gene encoding phosphoacetyltransferase is knocked out, then a gene encoding transcriptional anti-terminator and mRNA stability regulator is knocked out, then a gene encoding ATP-NAD kinase is integrated into a gene site encoding NADPH-dependent aldehyde reductase, and finally a gene promoter of acetyl-CoA synthetase is replaced by a Ptrc promoter to obtain the recombinant Escherichia coli. The recombinant Escherichia coli is used for fermentation to produce O-acetyl-L-homoserine, and has the advantage of high yield. metx artp patz cspc ppnk yahk acs ​​​​​​​

The application discloses a kind of recombination of Pseudomonas putida for producing L-lactic acid using whole-component lignocellulose hydrolysate and its construction method and application, belong to the field of metabolic engineering.The application uses Pseudomonas putida KT2440 as chassis, realizes carbon flow to pyruvic acid convergence and prevents product degradation by knocking out aceEF 、 ppsA And lldD Gene;By in-situ replacement, introduce optimized Lactobacillus plantarum ldhL1 Reconfiguration L-lactic acid synthesis pathway;By integration xylD-yjhH Tandem expression cassette enables xylose utilization;And by quorum sensing promoter P Rox306 Overexpression maeB Realize funnel conversion of lignin monomer.The application innovatively uses lignin derivatives in hydrolysate as natural donor of endogenous acetyl-coenzyme A, makes up lethal growth defect caused by knocking out aceEF The engineering bacteria of the application realize the synchronous high-efficiency conversion of glucose, xylose and aromatic monomer under the condition of not adding exogenous auxiliary carbon source and chemical inducer, which greatly reduces the industrial fermentation cost.

This invention provides an expression cassette, an expression vector, a genetically engineered strain, and their application in the preparation of malonic acid. The expression cassette includes expression cassette 1, expression cassette 2, and expression cassette 3. Expression cassette 1 includes the gene for the mitochondrial 37S ribosomal protein mS47; expression cassette 2 includes the ACC1 gene, which incorporates a mitochondrial localization signal encoding gene at its 5' end; and expression cassette 3 includes the upstream homologous arm of an endogenous ACC1 gene, which incorporates a weak promoter at its 5' end. This invention, through the expression cassette, can promote an increase in the levels of mS47 and ACC1 in mitochondria, thereby promoting the synthesis pathway of acetyl-CoA-malonyl-CoA-malonic acid (ACEA), while simultaneously reducing the level of endogenous ACC1 in the cytoplasm, avoiding competitive effects on the mitochondrial ACEA synthesis pathway, and ultimately effectively increasing malonic acid production.

Abstract Disclosed are biosynthetic methods and engineered microorganism that enhance or improve the biosynthesis of hexamethylenediamine, caproic acid or caprolactam. The engineered microorganisms include selected aldehyde dehydrogenase activity. Abstract 1 / 10 wo 2020 / 219863 PCT / US2020 / 029793 +HO2C 5CoA 5CoA SUCCINYL-CoA ACETYL-CoA A A HO2C 5CoA E,F,G HO2C 002H 3-OXOADIPL-CoA 3-OXOADIPATE B H OH OH HO2C 5CoA HO2C 002H 3-HYDROXYADIPYL-CoA 3-HYDROXYDIPATE C 000000 HO2C 5CoA HO2C OO2H 3-CARBOXY-2-PENTENOYL-CoA 5-CARBOXY-2-PENTENOATE D K,L,M HOC 5CoA HO2C OO2H ADIPYL-CoA ADIPATE X N Y H Z HO2C HO2C OPO3 ADIPATE SEMIALDEHYDE ADIPYLPHOSPATE O,P HO2C NH 6-AMINOCAPROATE S Q,R CoAS NH NH T 6-AMINOCAPROYL-CoA CAPROLACTAM U H V,WNH2 H2N NH2 6-AMINOCAPROATE SEMIALDEHYDE HEXAMETYLENEDIAMINE Fig. 1 SUBSTITUTE SHEET (RULE 26) 20 26 20 48 92 24 J un 2 02 6 1 / 1 0 w o 2 0 2 0 / 2 1 9 8 6 3 P C T / U S 2 0 2 0 / 0 2 9 7 9 3 2 0 2 6 2 0 4 8 9 2 2 4 J u n 2 0 2 6 A 5 C o A E , F , G H O 2 C O O 2 H 3 - O X O A D I P L - C o A 3 - O X O A D I P A T E B H O H O H 5 C o A H O 2 C 0 0 2 H 3 - H Y D R O X Y D I P A T E C 000000 H O 2 C 5 C o A O O 2 H 3 - C A R B O X Y - 2 - P E N T E N O Y L - C o A J O O 2 H 5 C o A H O 2 C A D I P Y L - C o A A D I P A T E X N Y H Z H O 2 C H O 2 C O P O 3 A D I P Y L P H O S P A T E H O 2 C N H 6 - A M I N O C A P R O A T E S Q , R C o A S N H N H 2 T 6 - A M I N O C A P R O Y L - C o A C A P R O L A C T A M U H V , W N H H 2 N N H 2 6 - A M I N O C A P R O A T E S E M I A L D E H Y D E H E X A M E T Y L E N E D I A M I N E F i g . 1 S U B S T I T U T E S H E E T ( R U L E 2 6 )

This invention provides a recombinant acetyl-CoA carboxylase encoding gene and its applications. Mutations at positions 5374, 5229, 5335, 5336, and 5493 in the recombinant acetyl-CoA carboxylase encoding gene provided by this invention can induce more significant resistance in rice expressing this recombinant acetyl-CoA carboxylase. In particular, it shows a significant increase in resistance to seven ACCase inhibitors from three major chemically distinct classes: arbutin (APP), quizalofop-P-ethyl, quizalofop-P-ethyl, and flupyrflupyr; cyclohexenone (CHD), clethodim and clodinafop-P-ethyl; and neophenylpyrazoline (DEN), clodinafop-P-ethyl.

A genetically engineered microbe capable of producing isoprene from a carbon source and method related thereto include a first nucleic acid sequence encoding a first enzyme, wherein the first enzyme is configured to catalyze one or more steps of a conversion from the carbon source to acetyl coenzyme A (A-CoA), a second nucleic acid sequence encoding a second enzyme of a mevalonate (MVA) pathway, and a heterologous nucleic acid sequence encoding a third enzyme, wherein the third enzyme is configured to catalyzing an isoprene-producing chemical reaction.

The invention discloses a recombinant Yarrowia lipolytica engineering strain for producing abscisic acid and application of the recombinant Yarrowia lipolytica engineering strain, and belongs to the technical field of genetic engineering and bioengineering. According to the invention, heterologous synthesis of ABA is realized in the Yarrowia lipolytica, precursor supply is optimized by enhancing carbon flow in a metabolic pathway, the activity of key enzymes BcABA2 and BcABA3 is improved by adopting a semi-rational strategy, NADPH regeneration engineering is implemented to enhance the oxygen uptake ability of a strain, a cytoplasm-peroxisome engineering system is constructed, and the oxygen uptake ability of the strain is enhanced. The ABA synthesis is further enhanced by utilizing the characteristic of high-yield acetyl coenzyme A of peroxisome. According to the invention, fermentation conditions are further optimized, so that the ABA accumulation concentration of the constructed engineering strain in a 5 L bioreactor reaches 2554.36 mg / L, and the highest titer of ABA biosynthesis reported so far is created. The metabolic modification strategy provides important reference for biosynthesis of other terpenoids.

The invention discloses a choline acetylase (ChAT) sensor constructed on the basis of manganese dioxide nanosheets (MnO2NSs) and application of the choline acetylase (ChAT) sensor in lung cancer A549 cells. According to the method, MnO2NSs and oxidation-state TMB (oxTMB) are reduced at the same time through CoA, MnO2NSs are reduced into Mn < 2 + >, catalytic activity is lost, and TMB cannot be catalyzed to be oxidized into blue oxTMB. Along with the increase of the CoA concentration, the color of the solution becomes light, and the ultraviolet absorption peak at 652nm is reduced, so that the ultraviolet colorimetric detection of CoA is realized. In addition, the change of the color of the solution causes the change of R, G and B values, and the CoA detection by the smart phone is realized through the relationship between the B / G value and the CoA concentration. ChAT can catalyze choline and acetyl coenzyme A (Ac-CoA) to generate CoA, and detection of ChAT is indirectly realized according to signal change caused by the generated CoA. The alpha-NETA can inhibit the activity of ChAT and reduce the generation of CoA, so that the inhibition effect of the alpha-NETA is evaluated. The method is applied to analysis of ChAT content in lung cancer cells, and has the advantages of visualization, simplicity in operation, high sensitivity and good specificity.

The invention provides a construction method of a saccharomyces cerevisiae engineering strain for producing squalene by using xylose and application of the saccharomyces cerevisiae engineering strain, and belongs to the technical field of genetic engineering. Saccharomyces cerevisiae CEN.PK.2-1D is used as a starting strain, the intracellular metabolic flux is directly redirected to acetyl coenzyme A synthesis by constructing a complete xylose utilization pathway and accelerating the xylose utilization rate of an engineering strain, and meanwhile, a complete MVA pathway gene and a downstream squalene synthesis pathway gene are integrated, so that the synthesis efficiency of the acetyl coenzyme A is improved. Saccharomyces cerevisiae engineering bacteria capable of synthesizing squalene by taking xylose as a unique carbon source are constructed. When 20 g / L of xylose is taken as a substrate, the squalene yield of shake flask fermentation is about 1318.73 + / -59.37 mg / L. According to the invention, the substrate spectrum of intracellular acetyl coenzyme A and terpenoid synthesis is broadened, and a new idea is provided for synthesizing high-value chemicals by using a carbon source containing xylose.

The invention belongs to the field of insecticides and acaricides, and relates to a composition containing alanine-isoxazoline compounds and acaricides. The composition contains an active component A and an active component B, wherein the weight part ratio of the active component A to the active component B is (1: 100)-(100: 1); the active component A is selected from a compound I, a compound II or a stereoisomer thereof; the active component B is selected from inhibitors influencing the growth of chitin synthetase 1 (CHS1) mites, mitochondrial adenosine triphosphate (ATP) synthetase inhibitors, mitochondrial electron transfer complex (III) inhibitors, mitochondrial electron transfer complex (I) inhibitors, acetyl-CoA carboxylase inhibitors and mitochondrial electron transfer complex (II) inhibitors; a trifluoroethyl sulfide type acaricide or other types of insecticidal and acaricide; the composition disclosed by the invention has the advantages of obvious synergism, resistance delaying and the like, and can be used for preventing and treating various pests.

The invention discloses a high-stability anti-interference free fatty acid detection kit as well as a preparation method and application thereof, the kit comprises a reagent R1 and a reagent R2, the reagent R1 comprises a phosphate buffer solution, acetyl coenzyme A synthetase, coenzyme A, adenosine triphosphate, 4-aminoantipyrine and a cyclodextrin-metal organic framework nano stabilizer with the concentration of 5-20 mg / mL; and the reagent R2 is prepared from a Tris-HCl buffer solution, acetyl coenzyme A oxidase, peroxidase, N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and a cyclodextrin-metal organic framework nano stabilizer with the concentration of 2 to 10mg / mL. Through the CD-MOF nano material with the specific aperture, triple breakthrough of improving the enzyme stability, enhancing the interference resistance of a complex sample and optimizing the detection sensitivity is synchronously realized.

The invention discloses an application of an NAT10-ac4C-mitochondrial-acetyl-CoA regulation axis in diagnosis and treatment of mitochondrial dysfunction and related metabolic diseases, and belongs to the technical field of biology. The regulatory axis systematically regulates the expression of the nuclear coding mitochondrial gene in a physiological state, and maintains a metabolism steady state; the invention also provides a biomarker combination of the regulatory axis. The biomarker combination comprises NAT10 related indexes, ac4C modification level of nuclear coding mitochondrial gene mRNA and acetyl coenzyme A level, and can be used for diagnosis and prognosis evaluation of mitochondrial dysfunction and related metabolic diseases. Meanwhile, the invention further provides a drug screening method, a treatment method and related drug application based on the regulation axis, systematic diagnosis and universal treatment of mitochondrial dysfunction related diseases are achieved, and the regulation axis has important clinical transformation value.

The invention relates to the fields of biochemical engineering, synthetic biology and biological medicine, in particular to a gemmarene A synthetase mutant, a fusion protein, an engineering strain and application. According to the invention, the GASX-L1H2H3V436LH4 with the highest catalytic activity is successfully obtained by means of point mutation and structural domain substitution; compared with wild type LTC2 and HaGAS1, the enzyme has the advantages that the catalytic activity is obviously improved, the fusion protein HaGAS1GGGSERG20 is constructed through a flexible linker, and the beta-elemene synthesis efficiency is further improved; on the basis, by strengthening a cytoplasm MVA pathway and constructing a peroxisome MVA pathway, intracellular precursor substances and acetyl coenzyme A are fully utilized, and the yield of elemene is further increased; on the basis, genes related to grease metabolism are screened to find overexpressed TGL4, and the shake flask yield of elemene is further increased.