Aroma compounds

Abstract

The present invention relates to processes for the oxidation of sesquiterpenes comprising fused 5- and 7-membered rings using mutant Cytochrome P450 family 102A sub-family member (CYP102A) enzymes. The invention also relates to mutant CYP102A enzymes, polynucleotides encoding the enzymes, cells expressing the enzymes, transgenic animals or plants comprising the enzymes, and compounds produced by the processes.

Description

[0001]AROMA COMPOUNDS Field of the Invention The disclosure relates to processes for synthesising aroma compounds, and polypeptides for use in the process. Background of Invention Agarwood has been used for centuries as an incense material for religious worship and more recently, as a fragrance. Guaiane-derived compounds are significant contributors to the aroma of agarwood; of these, (–)-guaia-1(10),11-diene (Figure 1), also known as α- bulnesene or δ-guaiene, is the biological precursor to the C15 alcohol (–)-guaia-1(10),11- dien-15-ol (bulnesene-15-ol, 1; Figure 1), the C15 aldehyde (–)-guaia-1(10),11-dien-15-al (bulnesene-15-al, 2; Figure 1), the C15 carboxylic acid (–)-guaia-1(10),11-dien-15-oic acid (3; Figure 1), and the lactone (–)-guaia-1(10),11-dien-15,2-olide (5; Figure 1). Aldehyde 2 and lactone 5 have been identified as major components of the aroma of kanakoh, the highest quality agarwood from Aquilaria agollocha. Aldehyde 2 has a pleasant β-damascenone-like woody note with a touch of camphor while the 15,2-lactone 5 has a long-lasting woody and ambery aroma with orris sub notes. The C2 and C9 ketones guaia-1(10),11-dien-2-one (bulnesene-2-one) and guaia-1(10),11-dien-9-one (bulnesene-9-one), and the 1,10-epoxide are other bulnesene-derived compounds isolated from kanakoh. α-Guaiene and its derivatives guaiol and rotundone (Figure 1) are also found in agarwood essential oil. Hydroxylated products of α-bulnesene could have wider flavour, aroma and biological properties, for example, the 15,2-lactone belongs to the sesquiterpene lactone family of compounds which are known to have interesting biological properties. Due to high demand, excessive logging has caused agarwood to become endangered and it was listed in the IUCN Red List of Threatened Species as far back as 2006. Therefore, the biotransformation of α-bulnesene to the aldehyde 2 and the lactone 5 provides a more sustainable source for agarwood aroma compounds. α-Bulnesene-15-al (2) and the 15,2- lactone (5) have only been isolated and characterised from Aquilaria agollocha (agarwood) on a small scale due to the limited supply of agarwood. α-Bulnesene is a major component of patchouli oil. However, the agarwood enzymes responsible for the sequential oxidation of α- bulnesene to metabolites 2 – 5 of Figure 1 have not been identified; for example, the synthesis of the aldehyde 2 requires oxidation of alcohol 1 but not further oxidation to the acid 3, while lactone 5 is formed via C2 oxidation of acid 3 followed by cyclisation. There is a need for new methods for catalysing the selective oxidation of sesquiterpenes comprising fused 5- and 7-membered rings, such as α-bulnesene. Summary of Invention The inventors have surprisingly discovered that engineered variants of the cytochrome P450 monooxygenase enzyme P450BM3(CYP102A1) are capable of oxidising α- bulnesene (δ-guaiene) to produce the aroma compounds naturally found in agarwood. Specifically, the inventors have unexpectedly discovered that the monooxygenase enzyme can be used to sequentially oxidise the carbon at position 15 of δ-guaiene. The inventors have also engineered variants of CYP102A1 that are capable of oxidising δ-guaiene at position 2. Thus, the inventors have provided a significant contribution to the art by providing an efficient method for producing agarwood aroma compounds using engineered variants of cytochrome P450BM3. Accordingly, the invention provides a process for oxidising a sesquiterpene comprising fused 5- and 7-membered rings, comprising contacting said sesquiterpene with a mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing oxygenase activity and / or altering product selectivity of the mutant enzyme. The invention also provides a mutant CYP102A (Cytochrome P450 family 102A sub- family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid. The invention also provides a mutant CYP102A (Cytochrome P450 family 102A sub- family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 181, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. In addition, the invention provides a kit or composition comprising the mutant CYP102A enzyme of the invention capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid, and the mutant CYP102A enzyme of the invention capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15- oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The invention further provides a composition comprising one or both of the mutant CYP102A enzymes of the invention, and a sesquiterpene comprising fused 5- and 7- membered rings, such as a guaiene and / or a guaiene-15-oic acid. The invention also provides one or more polynucleotides encoding an enzyme of the invention. The one or more polynucleotides may be in the form of a vector. The invention also provides a cell which expresses an enzyme of the invention. The invention additionally provides use of one or more enzymes of the invention for oxidising a sesquiterpene comprising fused 5- and 7-membered rings. Brief Description of the Figures Figure 1 - Guaiane derivatives in agarwood essential oil. Rotundone and guaiol are formed from α-guaiene while the other compounds are derivatives of α-bulnesene (also known as δ-guaiene). The percentages in brackets are the concentrations of the key agarwood aroma compounds. Figure 2 - Bulnesene oxidation products generated by P450BM3variants. Figure 3 - Products from bulnesene oxidation catalysed by P450BM3variants and the conditions by which selectivity between these products can be controlled. Brief Description of Sequence Listing SEQ ID NO: 1 – CYP102A1 nucleotide sequence SEQ ID NO:2 – CYP102A1 amino acid sequence SEQ ID NO: 3 (CYP102A1, residues 1-470). SEQ ID NO: 4 (CYP102A2, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 5 (CYP102A3, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 6 (CYP102A4, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 7 (CYP102A5, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 8 (CYP102A6, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 9 (CYP102A7, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 10 (CYP102A8, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 11 (CYP102A9, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 12 (CYP102A10, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 13 (CYP102A11, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 14 (CYP102A12, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 15 (CYP102A13, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 16 (CYP102A14, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 17 (CYP102A15, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 18 (CYP102A16, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 19 (CYP102A25, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 20 (CYP102A26, P450 domain corresponding to 1-470 of CYP102A1). SEQ ID NO: 21 (Krac9955 (A.K.A. CYP102A18), P450 domain corresponding to 1- 470 of CYP102A1). SEQ ID NO: 22 (Krac0936 (A.K.A. CYP102A18), P450 domain corresponding to 1- 470 of CYP102A1). SEQ ID NO: 23 (CYP102B1, P450 domain corresponding to 1-470 of CYP102A1). Detailed Description The invention relates to a process for oxidising a sesquiterpene. The process comprises the step of contacting said sesquiterpene with a mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said mutant CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold. The mutant CYP102A enzyme comprises a substitution or substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions. These substitutions thereby enhance oxygenase activity and / or alter substrate selectivity and / or alter product selectivity of the mutant enzyme when compared to the wild-type enzyme; allowing the mutant CYP102A enzyme to oxidise substrates more efficiently than the wild-type enzyme. As used herein, the term “wild-type enzyme” typically refers to the CYP102A enzyme from which the mutant CYP102A enzyme is derived, e.g. the CYP102A enzyme without the substitutions described. Substrate The invention relates to the oxidation of a sesquiterpene comprising fused 5- and 7- membered rings. As used herein, a sesquiterpene is a molecule comprising 14 or 15 carbon atoms, typically 15 carbon atoms. The base structure for the sesquiterpene comprises the structure shown in formula I. Formula I The sesquiterpene comprising fused 5- and 7-membered rings may comprise one or more double bonds in the rings. The sesquiterpene may comprise one or more double bonds in the 5-membered ring, and / or one or more double bonds in the 7-membered ring. Preferably, the sesquiterpene comprises one or more double bonds in the 7-membered ring. The sesquiterpene may comprise at least one double bond between carbons 1 and 10 of the structure shown in formula I, i.e. formula II. Formula II The sesquiterpene comprising fused 5- and 7-membered rings are substituted at one or more positions with a carbon-containing group. The sesquiterpene comprising fused 5- and 7-membered rings are preferably substituted with one or more exocyclic carbon-containing groups. The sesquiterpene comprising fused 5- and 7-membered rings may comprise a carbon-containing group at one or more positions selected from carbons 4, 7 and 10. The carbon-containing group may be selected from a one-carbon group, a two-carbon group, a three-carbon group, a four-carbon group or a five-carbon group. The one-carbon group may be a methyl group. The two-carbon group may be an ethyl group. The ethyl group may be an ethenyl group. The three-carbon group may be a propyl group, such as an isopropyl group. The propyl group may be a propenyl group or an isopropenyl group. Preferably, the sesquiterpene comprising fused 5- and 7-membered rings is substituted at carbon 10 with a methyl group. Preferably, the sesquiterpene comprising fused 5- and 7- membered rings is not substituted at carbon 2, or is not substituted at carbon 2 with a carbon- containing group. Preferably, the sesquiterpene comprising fused 5- and 7-membered rings may be substituted at carbon 10 with a methyl group and is not substituted at carbon 2. The sesquiterpene comprising fused 5- and 7-membered rings may be substituted at carbon 4 with a methyl group. The sesquiterpene comprising fused 5- and 7-membered rings may be substituted at carbon 7 with a propyl group, such as an isopropyl group, and preferably an isopropenyl group. The sesquiterpene comprising fused 5- and 7-membered rings may be substituted at carbon 10 with a methyl group and at carbon 7 with a propyl group. The sesquiterpene may be further substituted at carbon 4 with a methyl group. The sesquiterpene is preferably not substituted at carbon 2, or is not substituted at carbon 2 with a carbon-containing group. The sesquiterpene may therefore comprise the structure shown in formula III, which is otherwise referred to as δ-guaiene, bulnesene or α-bulnesene interchangeably herein. Formula III The sesquiterpenes described herein may be further substituted with non-carbon atoms. For example, the carbons may be oxidised to form a double-bonds. The carbons may be oxidised to form an alcohol, an aldehyde, a ketone or a carboxylic acid. Any of the one-, two-, three-, four- or five-carbon groups discussed herein may be oxidised. For example, the one-carbon group may be -CH3, -CH2OH, -COH2or – COOH. The two- or three-carbon groups may for an alcohol, an aldehyde, a ketone or a carboxylic acid. The cyclic carbons may form an alcohol. In some cases, a sesquiterpene comprising fused 5- and 7-membered rings, such as δ-guaiene, may comprise a -CH3, -CH2OH, -CHO or -COOH group at carbon 10. In some cases, a sesquiterpene comprising fused 5- and 7-membered rings, such as δ- guaiene, may comprise an alcohol group at carbon 2. In some cases, a sesquiterpene comprising fused 5- and 7-membered rings, such as δ-guaiene, may comprise an alcohol group at carbon 2 and a -CH3, -CH2OH, -COH2or -COOH group at carbon 10. The sesquiterpene comprising fused 5- and 7-membered rings may be a guaiene, a cedrene, or a patchoulene. The guaiene may be α-guaiene or δ-guaiene, preferably δ-guaiene. In some cases as explained herein, the guaiene may be oxidised. For example, the guaiene may comprise an alcohol at carbon 2, i.e. a guaiene-2-ol, such as δ-guaiene-2-ol. The guaiene may comprise an alcohol, aldehyde or carboxylic acid at carbon 15, i.e. a guaiene- 15-ol, a guaiene-15-al, or a guaiene-15-oic acid, such as δ-guaiene-15-ol, δ-guaiene-15-al, or δ-guaiene-15-oic acid. The sesquiterpenes described herein may comprise various enantiomers and / or diastereomers. Unless otherwise indicated, all such enantiomers and / or diastereomers are encompassed by the claims. In some cases, the specific stereoisomer of δ-guaiene (3,8- dimethyl-5-prop-1-en-2-yl-1,2,3,3a,4,5,6,7-octahydroazulene) may be (3S,3aS,5R)-3,8- dimethyl-5-(prop-1-en-2-yl)-1,2,3,3a,4,5,6,7-octahydroazulene. Product The invention involves the oxidation of a sesquiterpene comprising fused 5- and 7- membered rings to a product. The inventors have surprisingly found that a CYP102A enzyme may be modified to allow it to oxidise the non-natural substrates for the enzyme, such as those discussed above. As described in the Examples, the mutant CYP102A enzymes described herein are capable of oxidising a sesquiterpene comprising fused 5- and 7- membered rings at a number of positions, such as at a carbon on the ring itself (position 2) and / or at exocyclic carbons as well (at least carbons 11, 12 and 15). The process may be for oxidising the sesquiterpene at a cyclic carbon, i.e. for producing an alcohol, ketone or epoxide at a cyclic carbon of the sesquiterpene. The cyclic carbon may be a cyclic carbon of the 5-membered ring, preferably at carbon 2 (Formula I). For example, the process may be for producing an alcohol at a cyclic carbon of the 5- membered ring, such as for producing an alcohol at carbon 2 (Formula I). Where the sesquiterpene comprises one or more double-bonds in the rings, the process may be for oxidising the double bond to form an epoxide. For example, the process may be for producing an epoxide at carbons 1 and 10 (Formula II). The process may be for oxidising the sesquiterpene at an exocyclic carbon, i.e. for producing an alcohol, aldehyde, carboxylic acid, ketone or epoxide at an exocyclic carbon, preferably an alcohol, aldehyde or carboxylic acid. Preferably, the sesquiterpene is substituted at carbon 10 (Formula I) with one or more exocyclic carbons, preferably a single exocyclic carbon, and the process may be for oxidising the exocyclic carbon(s) substituted at carbon 10 of the sesquiterpene. For example, the process may be for producing an alcohol, aldehyde and / or carboxylic acid at the exocyclic carbon(s) substituted at carbon 10 of the sesquiterpene, which may depend on the oxidation state of the substrate. The sesquiterpene may be substituted at carbon 7 (formula I) with one or more exocyclic carbons, preferably an isopropenyl group, and the process may be for oxidising the exocyclic carbon(s) substituted at carbon 7 of the sesquiterpene. For example, the process may be for producing an epoxide at the isopropenyl group substituted at carbon 7 of the sesquiterpene. The process may be for carrying out multiple oxidation reactions, such as combinations of those discussed above. For example, the process may comprise oxidation of the sesquiterpene at carbon 2 to an alcohol and / or one or more oxidation(s) of a single exocyclic carbon substituted at carbon 10 of the sesquiterpene to an alcohol, aldehyde and / or carboxylic acid. The process may comprise oxidation of a single exocyclic carbon substituted at carbon 10 of the sesquiterpene to an alcohol, aldehyde and / or carboxylic acid and oxidation of an isopropenyl group substituted at carbon 7 of the sesquiterpene to an epoxide. Preferably, the substrate is a guaiene, cedrene or patchoulene, more preferably a guaiene (such as δ-guaiene). The process may be for oxidising the guaiene at carbon 2 (Formula III) to an alcohol or ketone, preferably an alcohol. The process may be for oxidising the guaiene at carbon 15 (Formula III) to an alcohol, aldehyde or carboxylic acid. The process may be for oxidising the guaiene at carbons 11 and 12 (Formula III) to an epoxide. The process may be for oxidising the guaiene at carbon 2 (Formula III) to an alcohol and for oxidising the guaiene at carbon 15 (Formula III) to an alcohol, aldehyde or carboxylic acid, preferably a carboxylic acid. The process may be for oxidising the guaiene at carbons 2 and 15 (Formula III) to form a lactone. The process may be for oxidising the guaiene at (i) carbon 15 (Formula III) to an alcohol, aldehyde or carboxylic acid, (ii) carbons 11 and 12 (Formula III) to an epoxide and / or (iii) carbon 2 (Formula III) to an alcohol or ketone, preferably an alcohol. Accordingly, the process may be for producing a guaiene-15- ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-ol, a guaiene-2- ol-15-al, a guaiene-2-ol-15-oic acid, a guaiene-15,2-olide, a 11,12-epoxy-guaiene, a 11,12- epoxy-guaiene-15-ol, a 11,12-epoxy-guaiene-15-al, 11,12-epoxy-guaiene-15-oic acid, a 11,12-epox-yguaiene-2-ol, and / or a 11,12-epoxy-guaiene-15,2-olide, preferably a guaiene- 15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The guaiene-2-ol in any of the products discussed herein may be comprise both isomers, i.e. guaiene-2R-ol and guaiene-2S-ol. The guaiene-2-ol in any of the products discussed herein may be guaiene-2R-ol. The guaiene-2-ol in any of the products discussed herein may be guaiene-2S-ol. In some cases where the mutant enzyme is specific for oxidation at an exocyclic carbon substituted at position 10 of the sesquiterpene (e.g. at carbon 15 of a guaiene), the process may be for producing a guaiene-15-ol, a guaiene-15-al and / or a guaiene-15-oic acid. In some cases where the mutant enzyme is specific for oxidation at carbon 2, the process may be for producing a guaiene-2-ol, such as guaiene-2r-ol and / or guaiene-2s-ol. In some cases where the substrate is a guaiene-15-oic acid, the process may be for producing a guaiene-2- ol-15-oic acid and / or a guaiene-15,2-olide, particularly where the mutant enzyme is specific for oxidation at carbon 2. Typically, the process may comprise contacting said sesquiterpene with a first mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme as described herein to produce a first sesquiterpene oxidation product, and contacting said sesquiterpene with a second mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a second sesquiterpene oxidation product. In this case, the process may be for oxidising the sesquiterpene at one or more carbons, preferably two or more, as described herein. Typically, the process may be for oxidising a guaiene at carbon 2 to an alcohol and at carbon 15 to an alcohol, aldehyde or carboxylic acid, preferably a carboxylic acid. Accordingly, the process may be for producing a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al or a guaiene-2-ol-15-oic acid, preferably a guaiene-2-ol-15-oic acid. Preferably, the product is not oxidised at positions other than carbon 2 and 15. Where the process involves the production of a guaiene-2-ol-15-oic acid, the process may further be for producing a guaiene-15,2-olide (5, Figure 2). Accordingly, the process may further comprise acidifying and / or heating the oxidised sesquiterpene, i.e. acidifying and / or heating the guaiene-2-ol-15-oic acid. Acidifying may involve contacting the guaiene- 2-ol-15-oic acid with an acid. The pH of the reaction mixture may be reduced to pH 5 or lower, such as pH 4 or lower, pH 3 or lower or pH 2 or lower. The acid may be hydrochloric acid. Heating may comprise increasing the temperature of the reaction mixture to 30˚C or higher, preferably 40˚C or higher. Heating may be performed for 1 to 24 hours, such as 2 to 12 hours, 4 to 8 hours or about 4 hours. As used herein, the mutant CYP102A is “specific” for producing a particular product or group of products discussed herein if it converts a substrate to said product or group of products with a greater efficiency, for example as calculated by conversion (%) or turnover number, than other products or groups of products. For example, a mutant CYP102A enzyme comprising F87I and V26L substitutions (i.e. corresponding to Entry 9 in Table 2), can be considered specific for producing product 2 (bulnesene-15-al; Figure 2) or alternatively can be considered specific for producing a product oxidised at carbon 15 (all of products 1 to 3; Figure 2). When determining the efficiency of the enzyme to specifically produce a particular product or group of products, the conditions used are typically constant, and may be any of the conditions used in the Examples. For example, the experiment may be performed at 20˚C. The experiment may be performed with a 6-24 hour incubation (such as 6, 9, 12, 18 or 24 hours) of enzyme with substrate, i.e. prior to determination of the products produced. 2μM enzyme may be used. A substrate:enzyme ratio of 100:1 to 10000:1 may be used, although as explained herein, the substrate:enzyme ratio may impact the products produced. The experiments may be performed in the presence of glucose (e.g. 100 mM), NADP+(e.g. 4 μM) and glucose dehydrogenase (e.g. 4 U ml-1). Organic compounds may be analysed using gas chromatography. Enhanced oxygenase activity and / or altered product / substrate selectivity The mutant CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold. The mutant comprises one or more substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions to thereby enhance oxygenase activity and / or alter product selectivity of the mutant enzyme. The enhanced monooxygenase activity and / or altered product selectivity may be assessed with respect to the corresponding wild-type CYP102A enzyme. The enhanced monooxygenase activity and / or altered product selectivity may be assessed with respect to SEQ ID NO: 2. The enhanced monooxygenase activity and / or altered product selectivity may be assessed with respect to the starting CYP102A enzyme prior to mutation. Monooxygenases are enzymes that incorporate a single oxygen atom into substrates. Enhancing monooxygenase activity means to increase the rate at which a monooxygenase catalyses the incorporation of a single oxygen atom into substrates. By repeating the monooxygenase activity on the same substrate, more than one oxygen may ultimately be incorporated into the substrate. The enhanced monooxygenase activity may be enhanced incorporation of a single oxygen atom into a sesquiterpene comprising fused 5- and 7-membered rings, preferably a guaiene such as δ-guaiene, more preferably at carbon 2 and / or carbon 15 of a guaiene such as δ-guaiene. The enhanced monooxygenase activity may be enhanced incorporation of a single oxygen atom at a carbon corresponding to carbon 2 and / or carbon 15 of δ-guaiene. The enhanced monooxygenase activity may be enhanced incorporation of more than one oxygen atom, such as two oxygen atoms, into a sesquiterpene comprising fused 5- and 7- membered rings, preferably a guaiene such as δ-guaiene, more preferably at carbon 15 of a guaiene such as δ-guaiene. In this case, the monooxygenase activity is processive, i.e. a single oxygen atom is incorporated at a time. The enhanced monooxygenase activity may be enhanced incorporation of two oxygen atoms at a carbon corresponding to carbon 15 of δ- guaiene. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene, such as δ-guaiene, to a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2- olide. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene, such as δ-guaiene, to a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene-2-ol, such as δ-guaiene-2-ol, to a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene-15-ol, such as δ-guaiene- 15-ol, to a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene-15-al, such as δ-guaiene-15-al, to a guaiene-15-oic acid, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The enhanced monooxygenase activity may be enhanced oxidation of a guaiene-15-oic acid, such as δ-guaiene-15-oic acid, to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. Enhanced monooxygenase activity may be characterised in terms of an increased conversion of substrate or an increased turnover number with sesquiterpenes as described herein for oxidation. The increased substrate conversion or increased turnover number may or may not be shared across all sesquiterpenes comprising fused 5- and 7-membered rings utilised by the mutant CYP102A enzyme. The mutant CYP102A enzyme typically displays a substrate conversion which is at least 10%, 20%, 50%, 100%, 500%, 1000%, 2000%, 5000%, 10000% greater than that of the wild type enzyme. The mutant CYP102A enzyme may also have a turnover number which is at least 50%, 100%, 150%, 500%, 1000%, 2000%, 5000%, 10000% greater than that of the wild type enzyme. The mutant CYP102A enzyme displays altered substrate specificity, allowing preferential utilization of sesquiterpene comprising fused 5- and 7-membered rings, whereas the wild type enzyme and known mutants are not able to oxidize sesquiterpene comprising fused 5- and 7-membered rings. The mutant CYP102A enzyme display altered product selectivity, i.e. new products not formed at all by the wild type enzyme become the majority or dominant product. Further altered characteristics of the mutant enzymes and of the oxidation processes carried out by the mutant enzymes are described below. Typically, the new product features (i) an alcohol at carbon 2, (ii) an alcohol, an aldehyde or a carboxylic acid at carbon 15 of δ-guaiene or a carbon corresponding to carbon 15 of δ-guaiene, and / or (iii) a carbon-15 to carbon 2 olide of δ-guaiene or an olide corresponding to a carbon-15 to carbon 2 olide of δ-guaiene. In some cases, the new product may feature an oxidation product at carbons 11 and / or 12 of δ-guaiene or at carbons corresponding to carbons 11 and / or 12 of δ-guaiene (such as an 11,12-epoxy group). The mutant enzyme has altered substrate selectivity. Altered substrate selectivity is where a wild-type CYP102A enzyme has been modified to increase or decrease binding affinity for compounds at the active site of the enzyme. For example, the CYP102A enzyme may be modified to increase binding affinity for sesquiterpenes comprising fused 5- and 7- membered rings, preferably a guaiene, a cedrene or a patchoulene, more preferably δ-guaiene (which includes alcohol, aldehyde, carboxylic acid and epoxy derivatives thereof), at the active site of the enzyme. The CYP102A enzyme may be modified to decrease binding affinity for non-desired substrates, such as the natural substrates for the enzyme, fatty acids or sesquiterpenes that do not comprise fused 5- and 7-membered rings, at the active site of the enzyme. As described in the Examples, the substrate:enzyme ratio plays a role in determining which oxidation product is produced, i.e. product selectivity. This is particularly true for the conversion of a guaiene to guaiene-15-ol, guaiene-15-al or guaiene-15-oic acid. The inventors have found that smaller substrate:enzyme ratios increase yield and / or enhance specificity for the guaiene-15-oic acid product. In contrast, large substrate:enzyme ratios increase yield and / or enhance specificity for the guaiene-15-ol and / or guaiene-15-al products. Accordingly, the process may utilise a substrate:enzyme ratio of 1000:1 or greater, preferably 2000:1 or greater, 4000:1 or greater or 8000:1 or greater, for example where the production of guaiene-15-ol and / or guaiene-15-al products is desired. In other embodiments, the process may utilise a substrate:enzyme ratio of 1000:1 or less, preferably 500:1 or less, for example, where the production of a guaiene-15-oic acid product is desired (such as where further oxidation at carbon to produce a guaiene-2-ol-15-oic acid or a guaiene-15,2-olide is desired). Heme monooxygenase domain comprising a P450 fold The mutant CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold. The heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 39.8% identity to amino acid residues 1–456 of SEQ ID NO: 2. Preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 40%, 41.6%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 1–456 of SEQ ID NO: 2. More preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 1–456 of SEQ ID NO: 2. The heme monooxygenase domain comprising a P450 fold may comprise amino acid residues 1–456 of SEQ ID NO: 2. Amino acid residues 1-456 of SEQ ID NO:2 include the complete P450 fold of the monooxygenase domain. It has been suggested that the monooxygenase domain may be considered to be amino acid residues 1-470 of SEQ ID NO: 2 (see Peterson et al. Steroids, 1992, 62, 117-123). Accordingly, in some embodiments, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 39.8% identity to amino acid residues 1–470 of SEQ ID NO: 2. Preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 40%, 41.6%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 1–470 of SEQ ID NO: 2. More preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 1–470 of SEQ ID NO: 2. The heme monooxygenase domain comprising a P450 fold may comprise amino acid residues 1–470 of SEQ ID NO: 2. Amino acid residues 1–470 of SEQ ID NO: 2 are set out in SEQ ID NO: 3. The heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 39.8% identity to SEQ ID NO: 3, for example, the sequences as set out in SEQ ID NOs: 3-22. Preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 40%, 41.6%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to SEQ ID NO: 3. More preferably, the heme monooxygenase domain comprising a P450 fold may comprise a sequence having at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to SEQ ID NO: 3. The heme monooxygenase domain comprising a P450 fold may comprise SEQ ID NO: 3. Reductase domain Preferably, the mutant CYP102A enzyme is a fusion of the heme monooxygenase domain to a reductase domain. The reductase domain typically transfers one or more electrons from a reducing agent, such as NADH or NADPH, to the heme of the monooxygenase domain comprising the P450 fold. The reductase domain may comprise one or more cofactors to shuttle one or more electrons from the reducing agent to the heme, such as FAD and FMN or a ferredoxin or a flavodoxin. The reductase domain may comprise or consist of a naturally occurring reductase or a domain that has at least 40% identity with a naturally occurring reductase, such as at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity. The reductase domain may comprise or consist of a reductase domain of any electron transfer chain found in naturally occurring P450 systems. The reductase domain may be a diflavin electron transfer domain, which contains both FAD and FMN prosthetic groups in a single polypeptide. The reductase domain may comprise or consist of a cytochrome P450 reductase (CPR) domain, such as a prokaryotic CPR domain or a eukaryotic CPR domain. The reductase domain may comprise a flavin-dependent reductase domain, such as a putidaredoxin reductase. The reductase domain may comprise an FAD-containing reductase domain, such as a prokaryotic FAD-containing reductase domain, and a ferredoxin or flavodoxin. The reductase domain may comprise or consist of an electron transfer redoxin that is able to mediate the transfer of electrons from a reducing agent, such as NADPH, NADH or FADH, to the heme of the monooxygenase domain comprising a P450 fold. The electron transfer redoxin may be a naturally occurring electron transfer redoxin or a protein that has at least 40% identity with a naturally occurring electron transfer redoxin, such as at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity. The electron transfer redoxin is typically a redoxin of any electron transfer chain found in naturally occurring P450 enzyme systems. The electron transfer redoxin is typically a 2Fe-2S redoxin, such as putidaredoxin, or a flavodoxin. The reductase domain may comprise a sequence having at least 40% identity to amino acid residues 471–1048 of SEQ ID NO: 2. Preferably, the reductase domain may comprise a sequence having at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 471–1048 of SEQ ID NO: 2. More preferably, the reductase domain may comprise a sequence having at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to amino acid residues 471–1048 of SEQ ID NO: 2. The reductase domain may comprise amino acid residues 471–1048 of SEQ ID NO: 2. It is understood that the reductase domain of CYP102A1 mediates the transfer of two electrons from NADPH to the heme in the P450 monooxygenase domain for the activation of dioxygen and formation of the ferryl, Compound I species that oxidises the substrate’s C-H bond. The amino acid substitutions discussed herein typically alter the binding orientation of the substrate to present a specific target C-H bond to the ferryl species, leading to higher activity and selectivity. These substitutions do not affect the mechanism of the formation of the ferryl species. Accordingly, pathways could be utilised to generate the ferryl species of a mutant CYP102A enzyme variant with the required product selectivity and provide substrate oxidation without the reductase domain, or NADPH or oxygen being present. One example is the conversion of CYP102A1 to a peroxygenase by the mutation T268E, such that the heme with the iron centre in the Fe(III) state can be converted to the ferryl species with hydrogen peroxide to effect substrate oxidation - the reductase domain, NADPH and dioxygen are not required (Shoji et al., Catal. Sci. Technol. 2016, 6, 5806–5811). Other substitutions such as T268D and T268H also allow the CYP102A1 enzyme to function as a peroxygenase. Addition of the T268E mutation to the heme domain of the mutant CYP102A enzymes disclosed herein having the ability to oxidise a sesquiterpene comprising fused 5- and 7-membered rings, would, for example, provide an alternative system for oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene- 2-ol-15-oic acid and / or a guaiene-15,2-olide without a reductase domain. Accordingly, in some aspects the mutant CYP102A enzyme does not comprise a reductase domain. In such aspects, the process is carried out in the presence of a mechanism to form the ferryl species in the heme monooxygenase domain, for example, in the presence of hydrogen peroxide or in the presence of a separate polypeptide encoding a reductase domain as described herein. The mutant CYP102A enzyme may additionally comprise the substitution T268E / T268D / T268H in SEQ ID NO:2 or a corresponding substitution in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue 268 of SEQ ID NO: 2. Said substitution may be in addition to any of the other substitutions discussed herein. Mutant CYP102A enzyme The mutant CYP102A enzyme may be a mutant enzyme selected from CYP102A1, CYP102A2, CYP102A3, CYP102A4, CYP102A5, CYP102A6, CYP102A7, CYP102A8, CYP102A9, CYP102A10, CYP102A11, CYP102A12, CYP102A13, CYP102A14, CYP102A15, CYP102A16, CYP102A25, CYP102A26, Krac9955 and Krac0936, for which the heme monooxygenase domains corresponding to amino acids 1-470 of SEQ ID NO: 2 are as set out in SEQ ID NOs: 3-22, respectively. Preferably, the mutant CYP102A enzyme is a mutant CYP102A1 enzyme. The CYP102A1 enzyme may be a natural or artificial homologue of CYP102A1, for example, having at least 40% amino acid identity to SEQ ID NO: 2. More preferably, the mutant CYP102A1 enzyme have comprise a sequence having at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to SEQ ID NO: 2. Said homologues typically comprise amino acid sequences which correspond to (i.e. are homologous to or the same as) amino acid sequences in the heme monooxygenase domain of CYP102A1 (represented by amino acid positions 1–456 of SEQ ID NO: 2; or in some embodiments represented by amino acid positions 1-470 of SEQ ID NO:2). The CYP102A1 enzyme may comprise (or consist of) a sequence which has at least 40% identity to SEQ ID NO: 2 (the sequence of CYP102A1). The CYP102A1 enzyme may have any of the specified percentage homologies when compared to amino acid residues 1 to 456 of SEQ ID NO: 2. The CYP102A1 enzyme may have any of the specified percentage homologies when compared to amino acid residues 1 to 470 of SEQ ID NO: 2. The homologous sequence may represent a mutated portion of the CYP102A1 sequence and / or may be present in the form of the full-length fusion disclosed herein. Homology can be measured using known methods. For example, the UWGCG Package provides the BESTFIT program which can be used to calculate homology (for example used on its default settings) (Devereux et al. Nucleic Acids Res. 1984, 12, 387–395). The PILEUP and BLAST algorithms can be used to calculate homology or line up sequences (typically on their default settings), for example, as described in Altschul S. F. (J. Mol. Evol. 1993, 36, 290–300) and in Altschul, S. F. et al. (J. Mol. Biol. 1990, 215, 403–410). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). Typically, the mutant CYP102A enzyme may comprise at least 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to amino acid residues 1–456 of SEQ ID NO:2. The mutant CYP102A enzyme may comprise no more than 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to amino acid residues 1–456 of SEQ ID NO:2. The mutant CYP102A enzyme may comprise at least 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to SEQ ID NO:2. The mutant CYP102A enzyme may comprise no more than 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to SEQ ID NO:2. The mutant CYP102A enzyme may comprise at least 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to amino acid residues 1–470 of SEQ ID NO:2. The mutant CYP102A enzyme may comprise no more than 1, 2, 5, 10, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200 or 220 mutations (each of which can be substitutions, insertions or deletions) when compared to amino acid residues 1–470 of SEQ ID NO:2. The enzymatic activity of the CYP102A enzyme of the invention is typically measured in vitro using any of the substrates or conditions mentioned herein and is typically given as the conversion rate (Conv; the percentage of substrate converted to products) and / or preferably, the turnover number (TON; the turnover number of the enzyme for producing the oxidised sesquiterpene). The conversion rate and / or turnover number is preferably measured when: - the sesquiterpene comprising fused 5- and 7-membered rings is a guaiene (preferably δ-guaiene) and the product is a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide; - the sesquiterpene comprising fused 5- and 7-membered rings is a guaiene-2-ol (preferably δ-guaiene-2-ol), and the product is a guaiene-2-ol-15-ol, a guaiene-2-ol-15-al, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide; and / or - the sesquiterpene comprising fused 5- and 7-membered rings is a guaiene-15-oic acid (preferably δ-guaiene-15-oic acid), and the product is a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The conversion rate and / or turnover number may be measured using a total of the desired oxidation products discussed herein, such as for the substrate / product combinations discussed above. For example, the conversion rate and / or turnover number of a guaiene (preferably δ-guaiene) may be measured using the total guaiene-15-ol, guaiene-15-al, guaiene-15-oic acid, guaiene-2-ol, guaiene-2-ol-15-ol, guaiene-2-ol-15-al, guaiene-2-ol-15- oic acid and guaiene-15,2-olide oxidation products produced. The conversion rate and / or turnover number of a guaiene (preferably δ-guaiene) may be measured using the total oxidation products at C15 only, e.g. guaiene-15-ol, guaiene-15-al, and guaiene-15-oic acid. The conversion rate and / or turnover number of a guaiene (preferably δ-guaiene) may be measured using the oxidation products at carbon 2 only, e.g. guaiene-2-ol. The conversion rate and / or turnover number of a guaiene (preferably δ-guaiene) may be measured using the total of certain oxidation products at carbons 2 and 15, e.g. guaiene-2-ol, guaiene-15-ol, guaiene-15-al, guaiene-15-oic acid, guaiene-2-ol-15-oic acid and guaiene-15,2-olide. In some cases, other oxidation products, such as the 11,12-epoxy oxidation products of δ- guaiene may be included in the calculation of TON and / or conversion rate. The conversion rate is typically measured at a substrate:enzyme ratio of e.g. 500:1, 1000:1, 2000:1 and / or 5000:1. As discussed herein, the substrate:enzyme ratio plays an important role into the oxidation state of the carbon 15 of δ-guaiene. The mutant CYP102A enzyme (for example when used in the process of the invention) may have a conversion rate of at least 10%, such as at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or more. The mutant CYP102A enzyme may have a turnover number of at least 50, such as at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 1000, at least 2000, at least 3000, at least 4000, at least 5000 or more. The mutant CYP102A enzyme may have a conversion rate of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90%, and a TON of at least 50. The mutant CYP102A enzyme may have a conversion rate of at least 10% and a TON of at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 2000, at least 3000, at least 4000 or at least 5000. The mutant CYP102A enzyme may have a conversion rate of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90%, and a TON of at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 2000, at least 3000, at least 4000 or at least 5000. The mutant CYP102A enzyme may comprise a sequence having at least 40% identity to SEQ ID NO: 2. Preferably, the mutant CYP102A enzyme may comprise a sequence having at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to SEQ ID NO: 2. More preferably, the mutant CYP102A enzyme may comprise a sequence having at least 80%, 85%, 90%, 95%, 95%, 97% or 99% identity to SEQ ID NO: 2. The mutant CYP102A enzyme may comprise SEQ ID NO: 2. Where specific mutants of CYP102A are described, the letter of the amino acid residue present in the wild-type form of CYP102A is followed by the position, followed by the amino acid in the mutant. These positions can be correlated to the numbering shown in SEQ ID NO:2. To denote multiple mutations in the same protein each mutation is listed separated by slashes. Particularly preferred mutants may be described using the entry numbers provided in Tables 1 to 9 of the examples. While mutations are defined by reference to a position in CYP102A1, the invention also encompasses equivalent substitution mutations at a homologous or corresponding position in the polypeptide chain of a homologue of CYP102A which shares at least 39.8% amino acid identity to SEQ ID NO:2. An equivalent position is determined by reference to amino acids 1–456 of SEQ ID NO:2. The homologous or corresponding position can be readily deduced by lining up the sequence of the homologue and the sequence amino acids 1– 456 of CYP102A1 (SEQ ID NO:2) based on the homology between the sequences. The PILEUP and BLAST algorithms can be used to line up the sequences. Where the homologous or corresponding amino acid referred to is an active site residue, it will generally be in a similar place in the active site of the homologue as any of the specific amino acids discussed herein. Despite having a highly conserved tertiary structure, the P450 superfamily of enzymes is well known to those skilled in the art to be unusual among proteins and enzymes in having primary structures with low homology. P450 enzymes in different families have amino acid identities as low as 20%. A sample of alignment between CYP102A1 and structurally characterized P450 enzymes is shown in Table A. In the systematic classification of the P450 superfamily, enzymes with just 40% amino acid identity are placed within the same family, and closely related members of a family (>55% identity) are grouped into sub- families (see, for example, Table B). It is increasingly recognized that the 40% cut-off for assigning enzymes to the same family could be too high in some instances, and that enzymatic activity and the higher homology often observed for active site residues may need to be taken more into consideration in future. Thus, enzymes that comprise a sequence having at least 40% amino acid identity to CYP102A1 (SEQ ID NO:2) are also be readily identifiable on the basis of the “P450 fold”, and alignment of sequences of homologues to introduce an equivalent mutation at a corresponding or homologous position may be assisted by knowledge of the conserved nature of the arrangement of α helices and β strands that comprises the P450 fold shared throughout the enzyme family. Table A. Sequence similarities between CYP102A1 heme domain (amino acid residues 1-470) and various structurally characterized cytochrome P450 enzymes. Cytochrome P450 CYP102A1 Identities Positives Gaps CYP505 (P450foxy) 188 / 452 (41%) 268 / 452 (59%) 10 / 452 (2%) CYP3A4 114 / 395 (28%) 184 / 395 (45%) 37 / 395 (9%) CYP51 (M. tuberculosis) 100 / 410 (24%) 180 / 410 (43%) 27 / 410 (6%) P4502R1 76 / 252 (30%) 126 / 252 (50%) 19 / 252 (7%) CYP175A1 98 / 364 (26%) 150 / 364 (41%) 61 / 364 (16%) CYP2D6 59 / 232 (25%) 96 / 232 (41%) 24 / 232 (10%) CYP2A6 99 / 434 (22%) 174 / 434 (40%) 26 / 434 (5%) CYP108A1 (P450terp) 58 / 219 (26%) 97 / 219 (44%) 30 / 219 (13%) CYP2A13 99 / 437 (22%) 170 / 437 (38%) 26 / 437 (5%) CYP2C8 57 / 198 (28%) 85 / 198 (42%) 7 / 198 (3%) CYP107L1 (P450pikC) 6 / 236 (27%) 102 / 236 (43%) 52 / 236 (22%) CYP2B4 55 / 229 (24%) 102 / 229 (44%) 13 / 229 (5%) CYP2C9 51 / 177 (28%) 80 / 177 (45%) 6 / 177 (3%) CYP2C5 49 / 165 (29%) 76 / 165 (46%) 6 / 165 (3%) CYP165B3 (P450oxyB) 75 / 324 (23%) 127 / 324 (39%) 63 / 324 (19%) CYP154C1 59 / 216 (27%) 84 / 216 (38%) 38 / 216 (17%) CYP154A1 70 / 343 (20%) 138 / 343 (40%) 53 / 343 (15%) CYP245A1 47 / 179 (26%) 74 / 179 (41%) 34 / 179 (18%) CYP119A1 51 / 180 (28%) 80 / 180 (44%) 45 / 180 (25%) CYP8A1 46 / 157 (29%) 72 / 157 (45%) 24 / 157 (15%) CYP167A1 (P450epoK) 51 / 219 (23%) 94 / 219 (42%) 38 / 219 (17%) CYP107A1 (P450eryF) 65 / 283 (22%) 114 / 283 (40%) 36 / 283 (12%) CYP199A2 43 / 176 (24%) 73 / 176 (41%) 27 / 176 (15%) CYP101A1 (P450cam) 56 / 223 (25%) 90 / 223 (40%) 57 / 223 (25%) CYP165C1 (P450oxyC) 48 / 204 (23%) 90 / 204 (44%) 41 / 204 (20%) CYP119A2 44 / 166 (26%) 70 / 166 (42%) 35 / 166 (21%) CYP152A1 (P450BSβ)41 / 148 (27%) 62 / 148 (41%) 20 / 148 (13%)CYP121 44 / 184 (23%) 72 / 184 (39%) 35 / 184 (19%) Table B. Sequence similarities between the CYP102A1 heme domain (amino acid residues 1– 470 of SEQ ID NO:2) and those of other CYP102A subfamily members. Note that, despite being in the same subfamily, CYP102A25 is only 39.8% homologous to CYP102A1, this homology being almost the same as between CYP102A1 and CYP102B1 from another CYP102 sub-family. Cytochrome P450 CYP102A1 Identities Positives Gaps CYP102A2 63.5% 75.5% 5.2% CYP102A3 64.3% 77.7% 2.3% CYP102A4 62.6% 76.6% 6.1% CYP102A5 65.2% 78.8% 2.8% CYP102A6 50.3% 66.0% 3.6% CYP102A7 64.5% 78.7% 2.3% CYP102A8 63.0% 76.8% 6.1% CYP102A9 63.9% 77.2% 6.1% CYP102A10 51.9% 67.6% 3.2% CYP102A11 52.9% 68.2% 2.8% CYP102A12 50.0% 64.9% 5.6% CYP102A13 48.9% 64.9% 4.8% CYP102A14 48.9% 64.9% 4.8% CYP102A15 58.5% 74.3% 2.3% CYP102A16 63.0% 76.8% 6.1% CYP102A18 (Krac9955) 44.9% 61.1% 6.9% CYP102A18 (Krac0936) 54.1% 71.1% 2.8% CYP102A25 39.8% 57.7% 6.5% CYP102A26 64.1% 77.5% 4.8% CYP102B1 39.7% 53.6% 17.5% It is to be understood that members of the CYP102A family are fusions of an electron transfer reductase domain and a heme monooxygenase domain. These domains may be cleaved proteolytically or by truncation of the full-length gene. The active site (substrate binding pocket) is located in the heme domain. Some members of the CYP102 family are not fusion proteins but the sequence homology with the CYP102A heme domain is 40%. Thus, sequence homology may be measured solely over the heme domain in these circumstances. Equivalent residues in these enzymes to those in CYP102A disclosed herein can be identified by sequence homology and structural analysis known to those skilled in the art. An amino acid in the active site is one which lines or defines the site in which the substrate is bound during catalysis or one which lines or defines a site through which the substrate must pass before reaching the catalytic site. Therefore, such an amino acid typically interacts with the substrate during entry to the catalytic site or during catalysis. Such an interaction typically occurs through an electrostatic interaction (between charged or polar groups), hydrophobic interaction, hydrogen bonding or van der Waals forces. Active site amino acids can be identified by sequence alignment and reference to the known crystal structure of the heme domain of wild type CYP102A, or the crystal structure of the homologues. Where the mutated residue is not an active site residue, computerized or manual alignment of sequences of the homologue and of CYP102A1 may be carried out to deduce the homologous or corresponding position, which may be assisted by knowledge of the residues flanking the mutated position in CYP102A1 set out in SEQ ID NO:2. Thus, for example, the 10 N-terminally and C-terminally flanking residues to the following positions in CYP102A1 are: CDESRFDKNL(S72)QALKFVRDFA DKNLSQALKF(V78)RDFAGDGLFT SQALKFVRDF(A82)GDGLFTSWTH FVRDFAGDGL(F87)TSWTHEKNWK DQPHPFITSM(V178)RALDEAMNKL ITSMVRALDE(A184)MNKLQRANPD DDENIRYQII(T260)FLIAGHETTS NIRYQIITFL(I263)AGHETTSGLL IRYQIITFLI(A264)GHETTSGLLS IITFLIAGHE(T268)TSGLLSFALY LNEALRLWPT(A328)PAFSLYAKED EYPLEKGDEL(M354)VLIPQLHRDK DHTNYELDIK(E435)TLTLKPEGFV Conservation of 2, 3 or more of the N- and / or C-terminal flanking residues can allow for deduction of the homologous or corresponding position at which a mutation is to be introduced. Similar analyses can be carried out for any other positions in CYP102A1 that are referred to in the description so as to identify the homologous or corresponding site in a naturally occurring homologue. The nature of the amino acid to be substituted at the positions of CYP102A described herein (or equivalent positions as defined above) is primarily determined by the requirement for the mutant to display an enhanced monooxygenase activity and / or altered product specificity. Thus, an amino acid that is introduced will typically enhance monooxygenase activity and / or alter product specificity. Where any reference is made to specific substitutions in CYP102A, it is to be understood that any substitution of another amino acid residue at the same position which has effects which are redundant over, or similar to, the effect of the specific substitution on the oxidation activity and / or product specificity of the CYP102A enzyme, is encompassed according to the present invention. Similarly, where a specific substitution also has an effect on another parameter of the CYP102A enzyme, such as substrate specificity, it is to be understood that substitutions of other amino acid residues that also elicit a redundant or similar effect are also contemplated for use according to the invention. In some embodiments, the substitution introduces a conservative change, which replaces the amino acid with another amino acid of similar chemical structure, similar chemical properties or similar side-chain volume. The amino acids introduced may have similar polarity, hydrophilicity or hydrophobicity to the amino acids they replace. Conservative amino acid changes are well known in the art and may be selected in accordance with the changes defined in table C. Where amino acids have similar polarity, this can also be determined by reference to the hydropathy scale for amino acid side chains (table D). The side chain volumes of the twenty naturally occurring amino acids may be grouped (from smallest to largest) as follows: Gly, Ala, Ser, Cys, Thr ≈ Asp ≈ Pro ≈ Asn, Val ≈ Glu ≈ Gln ≈ His, Ile ≈ Leu ≈ Met ≈ Lys, Phe ≈ Arg ≈ Tyr ≈ Trp. Table C. Physical characteristics of amino acids Ala aliphatic, hydrophobic, neutral Met hydrophobic, neutral Cys polar, hydrophobic, neutral Asn polar, hydrophilic, neutral Asp polar, hydrophilic, charged (-) Pro hydrophobic, neutral Glu polar, hydrophilic, charged (-) Gln polar, hydrophilic, neutral Phe aromatic, hydrophobic, neutral Arg polar, hydrophilic, charged (+) Gly aliphatic, neutral Ser polar, hydrophilic, neutral His aromatic, polar, hydrophilic, Thr polar, hydrophilic, neutral charged (+) Ile aliphatic, hydrophobic, neutral Val aliphatic, hydrophobic, neutral Lys polar, hydrophilic, charged (+) Trp aromatic, hydrophobic, neutral Leu aliphatic, hydrophobic, neutral Tyr aromatic, polar, hydrophobic Table D. Hydropathy scale ___________________________________________ Side Chain Hydropathy ___________________________________________ Ile 4.5 Val 4.2 Leu 3.8 Phe 2.8 Cys 2.5 Met 1.9 Ala 1.8 Gly -0.4 Thr -0.7 Ser -0.8 Trp -0.9 Tyr -1.3 Pro -1.6 His -3.2 Glu -3.5 Gln -3.5 Asp -3.5 Asn -3.5 Lys -3.9 Arg -4.5 Conservative amino acid changes may also be determined by reference to the Point Accepted Mutation (PAM) or BLOcks Substitution Matrix (BLOSUM) family of scoring matrices for conservation of amino acid sequence. Thus, conservative amino acid changes may be members of an equivalence group, being a set of amino acids having mutually positive scores in the similarity representation of the scoring matrix selected for use in an alignment of the reference and mutant polypeptide chains. It is to be understood that the definitions of physical characteristics provided in Table C are not considered to be limiting on the invention. For example, the amino acid proline is classified as non-polar but it also has the property of being rigid and can cause changes in secondary structure. For example, prolines are often found at the end of helices. Also, depending on the specific context of the side chain of a given amino acid residue, for example the amino acid tyrosine, generally classed as hydrophobic due to its aromatic ring, may have analogous functional effects to a polar amino acid residue such as threonine via its hydroxyl group. Thus, tyrosine may be considered to be both a hydrophobic and a polar amino acid for the purposes of the invention. Furthermore, amino acids which are described as polar or hydrophilic may be uncharged or charged, and may also be basic or acidic. The amino acid histidine is well known to have a pKa value near 7, so that at neutral pH depending upon the protein environment, it may or not be protonated on its side chain, and thus may or not carry a charge. Thus, histidine may be considered to be both a polar charged or a polar uncharged amino acid residue for the purposes of the invention. Substitutions The mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing monooxygenase activity and / or altering product selectivity of the mutant enzyme. The substitutions are typically in the heme monooxygenase domain comprising a P450 fold. The mutant CYP102A enzyme may comprise one or more substitution, such as two or more substitutions, three or more substitutions, four or more substitutions, five or more substitutions, six or more substitutions, seven or more substitutions, eight or more substitutions, nine or more substitutions or ten or more substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions to thereby enhancing monooxygenase activity and / or altering product selectivity of the mutant enzyme (i.e. substitutions that have an effect on the monooxygenase activity and / or product selectivity of the enzyme). For example, the mutant CYP102A enzyme may comprise one to twenty substitutions, such as one to ten substitutions, two to ten substitutions, three to ten substitutions, four to ten substitutions, five to ten substitutions, one to five substitutions, one to four substitutions, one to three substitutions or one or two substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions to thereby enhancing monooxygenase activity and / or altering product selectivity of the mutant enzyme. The substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme that thereby enhance monooxygenase activity and / or alter product selectivity of the mutant enzyme may be at one or more positions corresponding to amino acid residue positions 26, 71, 72, 74, 78, 82, 87, 88, 178, 181, 184, 260, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. The substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme that thereby enhance monooxygenase activity and / or alter product selectivity of the mutant enzyme may be selected from A82I, A82M, F87A, F87I, F87L, F87V, A184I, A184M, A184F, T260L, T260G, V26L, V26M, L71F, L71M, S72G, S72V, S72I, S72L, S72A, S72W, A74L, V78A, V78I, T88L, T88F, T88M, V178F, L181F, I263A, I263G, A264G, E267F, E267V, A328F, A328I, A328L, A330V, A330I, A330F, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2 or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme as one or more positions corresponding to the amino acid residues 26, 71, 72, 74, 78, 82, 87, 88, 178, 181, 184, 260, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. The substitution in the polypeptide chain at a position corresponding to amino acid residue 26 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 26 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 26 of SEQ ID NO: 2 may be a substitution selected from V26L and V26M of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 71 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 71 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 71 of SEQ ID NO: 2 may be a substitution selected from L71F and L71M of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 72 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 72 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 72 of SEQ ID NO: 2 may be a substitution with an aliphatic, neutral and optionally hydrophobic amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 72 of SEQ ID NO: 2 may be a substitution selected from S72G, S72V, S72I, S72L, S72A and S72W of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 78 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 78 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. More preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 78 of SEQ ID NO: 2 may be a substitution with an aliphatic, hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 78 of SEQ ID NO: 2 may be a substitution selected V78A and V78I of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 82 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 82 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 82 of SEQ ID NO: 2 may be a substitution selected from A82I and A82M of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 87 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 87 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. More preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 87 of SEQ ID NO: 2 may be a substitution with an aliphatic, hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 87 of SEQ ID NO: 2 may be a substitution selected from F87A, F87I, F87L and F87V of SEQ ID NO: 2 or a substitution corresponding thereto. In some cases, the substitution is not F87A or F87V. The substitution in the polypeptide chain at a position corresponding to amino acid residue 88 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 88 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 88 of SEQ ID NO: 2 may be a substitution selected from T88L, T88F and T88M of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 178 of SEQ ID NO: 2 may be a substitution with an aromatic amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 178 of SEQ ID NO: 2 may be a substitution with an aromatic, hydrophobic amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 178 of SEQ ID NO: 2 may be a substitution selected from V178F of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 181 of SEQ ID NO: 2 may be a substitution with an aromatic amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 181 of SEQ ID NO: 2 may be a substitution with an aromatic, hydrophobic amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 181 of SEQ ID NO: 2 may be a substitution selected from L181F of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 184 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 184 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 184 of SEQ ID NO: 2 may be a substitution selected from A184I, A184M and A184F of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 260 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 260 of SEQ ID NO: 2 may be a substitution with a aliphatic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 260 of SEQ ID NO: 2 may be a substitution selected from T260L and T260G of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 263 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 263 of SEQ ID NO: 2 may be a substitution with an aliphatic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 263 of SEQ ID NO: 2 may be a substitution selected from I263A and I263G of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 264 of SEQ ID NO: 2 may be a substitution with an aliphatic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 264 of SEQ ID NO: 2 may be a substitution selected from A264G of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 267 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 267 of SEQ ID NO: 2 may be a substitution with a non-polar, neutral amino acid. More preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 267 of SEQ ID NO: 2 may be a substitution with a non-polar, hydrophobic, neutral amino acid The substitution in the polypeptide chain at a position corresponding to amino acid residue 267 of SEQ ID NO: 2 may be a substitution selected from E267F and E267V of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 328 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 328 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 328 of SEQ ID NO: 2 may be a substitution selected from A328F, A328I and A328L of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 330 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 330 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 330 of SEQ ID NO: 2 may be a substitution selected from A330V, A330I, A330F, A330P and A330W, preferably A330V, A330I, A330F and A330W of SEQ ID NO: 2 or a substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 332 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue substitution corresponding thereto. The substitution in the polypeptide chain at a position corresponding to amino acid residue 437 of SEQ ID NO: 2 may be a substitution with a neutral amino acid. Preferably, the substitution in the polypeptide chain at a position corresponding to amino acid residue 437 of SEQ ID NO: 2 may be a substitution with a hydrophobic, neutral amino acid. The substitution in the polypeptide chain at a position corresponding to amino acid residue 437 of SEQ ID NO: 2 may be a substitution selected from L437V, L437F and L437M of SEQ ID NO: 2 or a substitution corresponding thereto. Any method known in the art may be used to determine if a mutant CYP102A enzyme is capable of oxidising a sesquiterpene comprising 5- and 7-membered ring. For example, any of the methods described in the Examples may be used. The method may comprise contacting the mutant CYP102A enzyme with the substrate. The reaction may be initiated with NADPH (e.g. provided directly or by providing NADP+, glucose and glucose dehydrogenase). A sample may be extracted, for example, using ethyl acetate. The sample may be analysed, for example, using gas chromatography (GC) or GC-mass spectrometry (GC-MS). The mutant CYP102A enzyme may comprise any of the substitutions in a row of Tables 1 to 9. The mutant CYP102A enzyme may comprise any of the substitutions in a row of Tables 1 to 9 without the ‘base’ mutations, i.e. without the K19, R19, RT2, RP or GVQ ‘base’ mutations. The mutant CYP102A enzyme may oxidise the substrate utilised in Table from which the substitutions are derived. The mutant CYP102A enzyme may produce one or more of the products described in the Table from which the substitutions are derived. The mutant CYP102A enzyme may specifically convert a substrate to a product or a group of related products if the product or group of products if produced in greater quantities than any other product. For example, a mutant CYP102A enzyme comprising F87I and V26L substitutions (i.e. corresponding to Entry 9 in Table 2), can be considered specific for producing product 2 (bulnesene-15-al; Figure 2) or alternatively can be considered specific for producing a product oxidised at carbon 15 (all of products 1 to 3; Figure 2). The substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme that thereby enhance monooxygenase activity and / or alter product selectivity of the mutant enzyme discussed herein broadly fall into two classes: suitable for oxidation at carbon 15 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 15 of a guaiene (such as δ- guaiene), and / or suitable for oxidation at carbon 2 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 2 of a guaiene (such as δ-guaiene). Other groups also exist, such as those suitable for oxidation at carbon 11 and / or 12 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 11 and / or 12 of a guaiene (such as δ-guaiene), and those suitable for oxidation at both carbons 2 and / or 15 of a guaiene (such as δ-guaiene) or a carbon corresponding to both carbons 2 and / or 15 of a guaiene (such as δ-guaiene). The mutant CYP102A enzymes disclosed herein may be suitable for oxidation at more than one of the groups discussed above. Oxidation at carbon 15 of a guaiene The mutant CYP102A enzyme may be suitable for oxidation at carbon 15 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 15 of a guaiene (such as δ- guaiene). Said mutant CYP102A enzyme preferably comprises a substitution at one or more positions corresponding to amino acid positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, preferably at one or more positions corresponding to amino acid positions 87, 82, 88, 184, 260 and / or 330 of SEQ ID NO: 2. Typically, the mutant CYP102A enzyme may comprise 2 or more, 3 or more, 4 or more, or 5 or more of the substitutions at positions corresponding to amino acid positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330, preferably 2 or more, 3 or more, 4 or more or five or more of the substitutions at positions corresponding to amino acid positions 87, 82, 88, 184, 260 and / or 330 of SEQ ID NO: 2. The one or more substitutions may be selected from A82I, A82M, F87I, A184I, A184M, A184F, T260L, T260G, V26L, V26M, L71M, S72V, S72I, S72L, S72A, S72W, A74L, V78I, T88L, T88F, T88M, L181F, I263A, I263G, E267V, A328I, A330V, A330I, A330F, A330P and / or A330W in SEQ ID NO:2, or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, preferably at one or more positions corresponding to amino acid positions 87, 82, 88, 184, 260 and / or 330 of SEQ ID NO: 2. The CYP102A enzyme may comprise one or the following groups of substitutions in SEQ ID NO:2: - F87I; - F87I / A330P; - A82M; - F87I / A184I / V26L; - A82M / T260G; - F87I / A184I / V26M; - A184I / T260G; - F87I / A184I / S72L; - A82M / A184I / T260G; - F87I / A184I / A82M; - F87I / V26L; - F87I / A184I / A330I; - F87I / V26M; - F87I / A184I / A330V; - F87I / L71M; - F87I / A82M / A330I; - F87I / S72V; - F87I / A82M / A330V; - F87I / S72I - F87I / A82M / A184I; - F87I / S72L; - F87I / A82M / A330I / A184I; - F87I / A74L; - F87I / A82M / A330V / A184I; - F87I / A82I; - F87I / A82M / A330I / V26L; - F87I / A82M; - F87I / A82M / A330V / V26L; - F87I / T88L; - F87I / A82M / A330I / V26M; - F87I / T88F; - F87A / A328I; - F87I / T88M; - F87A / A328I / S72A; - F87I / L181F; - F87A / A328I / S72W; - F87I / A184F; - F87A / A328I / V78I; - F87I / A184I; - F87L / I263G; - F87I / A184M; - A184I / A328L; - F87I / T260G; - E267V; - F87I / T260L; - E267V / I263A; - F87I / A330V; - E267V / V78I; - F87I / A330I; - A330W; - F87I / A330F; - A330W / S72G; or - F87I / A330W; - A330W / S72W; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed above. Oxidation at carbon 2 of a guaiene The mutant CYP102A enzyme may be suitable for oxidation at carbon 2 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 2 of a guaiene (such as δ-guaiene). Said mutant CYP102A enzyme preferably comprises a substitution at one or more positions corresponding to amino acid positions 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. Typically, the mutant CYP102A enzyme may comprise 2 or more, 3 or more, 4 or more, or 5 or more of the substitutions at positions corresponding to amino acid positions 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. In some cases, said mutant CYP102A enzyme may comprise a substitution at a position corresponding to amino acid residue position 87 of SEQ ID NO:2, and at one or more positions corresponding to amino acid residue positions 72, 78, 82, 178, 184, 263, 264, 267, 328, 330 and / or 437 of SEQ ID NO: 2. The one or more substitutions may be selected from F87A, F87L, F87V, L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M in SEQ ID NO: 2, or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. In some cases, said substitution may be a substitution selected from F87A, F87L, F87V, and one or more substitution(s) selected from L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at position 87 and at one or more positions corresponding to the amino acid residues 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. The CYP102A enzyme may comprise one or the following groups of substitutions in SEQ ID NO:2: - F87A / A184I; - F87A / A184I / I263G / A264G / A328G; - F87A / I263G; - F87A / A184I / I263G / A330P; - F87A / A330P; - F87A / A184I / I263G / A264G / A330P; - F87A / A184I / A330P - F87A / I263G / A264G; - F87A / I263G / A330P; - F87L / I263G; - F87A / A184I / I263G / A264G; - F87L / I263G / A328F; - F87A / A184I / I263G / A328G; - I263G - F87A / A328I; - I263G / S72G; - F87A / A328L; - I263G / S72W; - F87V / V78I; - I263G / A82M; - F87V / A264G; - I263G / A184I; - F87I / A82M / A184I / A330I / L71F; - I263G / A264G / A328G - F87I / A82M / A184I / A330I / L71M; - A330P; - F87I / A82M / A184I / A330I / V178F; - A330W; - F87I / A82M / A184I / A330I / V78A / - A330W / S72G; S332M; - A330W / A82M; or - F87I / A82M / A184I / A330I / L437F; - A330W / A82M / I263A - F87I / A82M / A184I / A330I / L437M; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed above. Oxidation at carbons 2 and 15 of a guaiene The mutant CYP102A enzyme may be suitable for oxidation at carbons 2 and 15 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbons 2 and 15 of a guaiene (such as δ-guaiene). Said mutant CYP102A enzyme preferably comprises a substitution at one or more positions corresponding to amino acid positions 87, 78, 82, 184, 330 and / or 332 of SEQ ID NO: 2. Typically, the mutant CYP102A enzyme may comprise 2 or more, 3 or more, 4 or more, or 5 or more, or all six of the substitutions at positions corresponding to amino acid positions 87, 78, 82, 184, 330 and / or 332 of SEQ ID NO: 2. The one or more substitutions may be selected from F87I, A82M, A184I, A330I, V78A and / or S332M in SEQ ID NO:2, or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues 87, 78, 82, 184, 330 and / or 332 of SEQ ID NO: 2. Preferably, the one or more substitutions comprises F87I, A82M, A184I, A330I, V78A and S332M in SEQ ID NO: 2. Oxidation at carbon 11 and / or 12 of a guaiene The mutant CYP102A enzyme may be suitable for oxidation at carbon 11 and / or 12 of a guaiene (such as δ-guaiene) or a carbon corresponding to carbon 11 and / or 12 of a guaiene (such as δ-guaiene). For example, the mutant CYP102A enzyme may be suitable for oxidation at carbon 11 and / or 12 of a guaiene-15-oic acid (such as δ-guaiene-15-oic acid). Said mutant CYP102A enzyme preferably comprises a substitution at one or more positions corresponding to amino acid positions 87, 26, 71, 82, 178, 184, 260, 263, 264, 328, 330, 332 and / or 437 of SEQ ID NO: 2. Typically, the mutant CYP102A enzyme may comprise 2 or more, 3 or more, 4 or more, or 5 or more of the substitutions at positions corresponding to amino acid positions 87, 26, 71, 82, 178, 184, 260, 263, 264, 328, 330, 332 and / or 437 of SEQ ID NO: 2. The one or more substitutions may be selected from F87A, F87I, V26L, V26M, L71F, L71M, A82M, V178F, A184I, T260G, I263G, A264G, A328G, A330F, A330I, A330P, A330V, S332M, L437V, L437M in SEQ ID NO:2, or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues 87, 26, 82, 184, 260, 263, 264, 328 and / or 330 of SEQ ID NO: 2. The CYP102A enzyme may comprise one or the following groups of substitutions in SEQ ID NO:2: - F87I; - F87I / A82M / A330I / V26L; - A82M / A184I / T260G; - F87I / A82M / A330V / V26L; - A184I / T260G; - F87I / A82M / A330I / V26M; - F87I / A330F; - F87A / A184I; - F87I / A184I / V26L; - F87A / I263G; - F87I / A184I / A330I; - F87A / A184I / A330P; - F87I / A184I / A330V; - F87A / A184I / I263G / A264G; - F87I / A82M / A330I; - F87A / A184I / I263G / A328G; - F87I / A82M / A184I; - F87A / A184I / I263G / A264G / A328G; - F87I / A82M / A330I / A184I; - F87A / A184I / I263G / A330P; - F87I / A82M / A330V / A184I; - F87A / A184I / I263G / A264G / A330P; - F87A / I263G / A264G; or - F87I / A82M / A330I / A184I / L171H / - F87A / I263G / A330P; V178F - F87I / A82M / A330I / A184I / L71F - F87I / A82M / A330I / A184I / S332M - F87I / A82M / A330I / A184I / L71M - F87I / A82M / A330I / A184I / L437V - F87I / A82M / A330I / A184I / L437M or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed above. Additional mutations The CYP102A enzyme may have 1, 2, 3, 4, 5 to 10, 10 to 20, 20 to 40 or more additional mutations, such as substitutions, insertions or deletions. These additional mutations may or may not enhance monooxygenase activity and / or alter product selectivity of the mutant CYP102A enzyme. The other mutations may be in the active site or outside the active site. For example, the mutations may be in the second sphere, i.e. residues which affect or contact the position or orientation of one or more of the amino acids in the active site. An insertion will typically be N and / or C terminal. Thus, the enzyme may contain a short peptide of up to 20 amino acids or a full-length protein fused to either or both of the termini, e.g. to aid protein purification by affinity chromatography or immobilisation on a solid matrix, such as via a histidine tag. A deletion typically comprises the deletion of amino acids which are not involved in catalysis, such as those outside the active site (thus the enzyme is a mutated fragment of a naturally occurring enzyme). Other mutations in the active site may alter the position and / or conformation of the substrate when it is bound in the active site. The mutations may make the site on the substrate which is to be oxidized more accessible to the heme group. Thus, the mutations discussed herein may be substitutions to an amino acid which has a smaller or larger, or more or less polar, side chain. The CYP102A enzyme may additionally comprise the K19, R19, RT2, RP or GVQ ‘base’ mutations. The K19 substitutions are H171L / Q307H / N319Y of SEQ ID NO: 2. The R19 substitutions are R47L / Y51F / H171L / Q307H / N319Y of SEQ ID NO: 2. The RT2 substitutions are R47L / Y51F / A191T / N239H / I259V / A276T / L353I of SEQ ID NO: 2. The RP substitutions are R47L / Y51F / I401P of SEQ ID NO: 2. The GVQ substitutions are A74G / F87V / L188Q of SEQ ID NO: 2. Preferably the additional substitutions are selected from the K19 or R19 substitutions. Accordingly, the CYP102A enzyme may additionally comprise the substitutions H171L, Q307H and N319Y of SEQ ID NO:2 or corresponding substitutions at positions corresponding to amino acid residue positions 171, 307 and 319 of SEQ ID NO: 2. The CYP102A enzyme may additionally comprise the substitutions R47L, Y51F, H171L, Q307H and N319Y of SEQ ID NO:2 or corresponding substitutions at positions corresponding to amino acid residue positions 47, 51, 171, 307 and 319 of SEQ ID NO: 2. Mutant CYP102A enzymes The invention also relates to a mutant CYP102A enzyme comprising a heme monooxygenase domain comprising a P450 fold, and said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2. The monooxygenase activity and / or altering product selectivity of the mutant enzyme is thereby enhanced when compared to the wild-type enzyme. The enzyme is suitable for oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid. The enzyme may be capable of oxidising other compounds, such as a sesquiterpene comprising fused 5- and 7-membered rings, other sesquiterpenes, terpenes and the like. The mutant enzyme may comprise the substitutions described herein in relation to the process of the invention. The wild-type CYP102A enzyme does not act as a monooxygenase for guaiene substrates, nor for sesquiterpenes comprising fused 5- and 7-membered rings. The invention also relates to a mutant CYP102A enzyme comprising a heme monooxygenase domain comprising a P450 fold, and said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 181, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. The monooxygenase activity and / or altering product selectivity of the mutant enzyme is thereby enhanced when compared to the wild-type enzyme. The enzyme is suitable for oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. The enzyme may be capable of oxidising other compounds, such as a sesquiterpene comprising fused 5- and 7-membered rings, other sesquiterpenes, terpenes and the like. The mutant enzyme may comprise the substitutions described herein in relation to the process of the invention. The wild-type CYP102A enzyme does not act as a monooxygenase for guaiene substrates, nor for sesquiterpenes comprising fused 5- and 7- membered rings. The mutant CYP102A enzyme (for example when used in the process of the invention) may have a conversion rate of at least 10%, such as at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or more. The mutant CYP102A enzyme may have a turnover number of at least 50, such as at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 1000, at least 2000, at least 3000, at least 4000, at least 5000 or more. The mutant CYP102A enzyme may have a conversion rate of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90%, and a TON of at least 50. The mutant CYP102A enzyme may have a conversion rate of at least 10% and a TON of at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 2000, at least 3000, at least 4000 or at least 5000. The mutant CYP102A enzyme may have a conversion rate of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90%, and a TON of at least 50, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 2000, at least 3000, at least 4000 or at least 5000. The mutant CYP102A enzyme may comprise one or more additional substitutions discussed above in relation to the process of the invention. Also provided is a process for oxidising an organic compound substrate, comprising the step of contacting said organic compound substrate with the mutant CYP102A enzyme of the invention. The organic compound is typically any organic compound capable of being oxidized by a monooxygenase enzyme. The suitability of any organic compound for oxidation by a monooxygenase enzyme may be routinely determined by the methods described herein. The organic compound may be a terpene, preferably a sesquiterpene, more preferably a sesquiterpene comprising fused 5- and 7-membered rings. The oxidation process causes the formation of a C–O bond in the compound, generally as the alcohol from the oxidation of a carbon-hydrogen bond, but an epoxide may be formed from the oxidation of a C=C bond. The oxidation may thus introduce an alcohol, aldehyde, ketone or epoxide group. Alternatively, the oxidation may cause the further oxidation of an oxygen containing group, such as converting an alcohol group into an aldehyde, ketone or carboxylic acid. 1, 2 or more carbon atoms may be attacked in the same substrate molecule. Oxidation can also result in N- and O-dealkylation of the substrate molecule. The substrate can either be a natural substrate of a wild type CYP102A enzyme or a substrate which is not normally a substrate for the wild type enzyme, but which is capable of being utilized as such in the mutant enzyme. Examples of natural substrates for CYP102A enzymes are branched and straight chain fatty acids, which are hydroxylated by wild type CYP102A1 at sub-terminal positions (ω-1 to ω-3). Preferred examples are lauric acid, undecanoic acid, decanoic acid, nonanoic acid and octanoic acid. Examples of non-natural substrates of a wild type CYP102A enzyme that may be utilized with the mutant CYP102A enzyme include sesquiterpenes comprising fused 5- and 7-membered rings, such as a guaiene, a cedrane or a patchoulene. Combinations The processes described herein may involve the use of two or more mutant CYP102A enzymes. For example, the process may comprise contacting said sesquiterpene with a first mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a first sesquiterpene oxidation product, and contact said first sesquiterpene oxidation product with a second mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a second sesquiterpene oxidation product. The first and second mutant CYP102A enzymes may be any of the mutant CYP102A enzymes described herein. For example, the first mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 15 and the second mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 2. Similarly, the first mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 2 and the second mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 15. The contacting steps may be performed sequentially or simultaneously. Typically, the contacting steps are performed in a single reaction mixture. Preferably, the contacting steps are performed simultaneously in a single reaction mixture, i.e. the process comprises contacting said sesquiterpene with a first mutant CYP102A enzyme and a second mutant CYP102A enzyme to produce a sesquiterpene oxidation product (i.e. a product which has been oxidised by both the first and second mutant CYP102A enzymes). As discussed in Example 5, the ratio of first and second mutant CYP102A enzymes may be optimised to reduce the production of oxidation by-products, such as the guaiene- 11,12-epoxides (9, 9a; Figure 2). Accordingly, the first mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 15 and the second mutant CYP102A enzyme may be suitable for oxidising a guaiene at carbon 2, and the ratio of first to second mutant CYP102A used in the process is 1:1 or more, such as 1:1.5 or more, 1:2 or more, 1:2.5 or more or 1:3 or more. Where specific substrate:enzyme ratios are used as discussed herein, the ratio is typically calculated as a substrate:first mutant CYP102A enzyme ratio (i.e. not counting the contribution from the second mutant CYP102A enzyme). The invention also relates to a kit or composition comprising one or more of the mutant CYP102A enzymes described herein. For examples, a kit or composition may comprise (a) a mutant CYP102A enzyme capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid, and (b) mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. Furthermore, a composition may comprise one or more of the mutant CYP102A enzymes described herein and a sesquiterpene comprising fused 5- and 7-membered rings. The composition may therefore comprise (a) a mutant CYP102A enzyme capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid, and (b) mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene- 15,2-olide. The sesquiterpene comprising fused 5- and 7-membered rings may be any of the substrates described herein, such as a guaiene and / or a guaiene-15-oic acid. Other products of the invention The process may comprise a further step of formulating the oxidised sesquiterpene (produced according to a process described herein) in a fragrance, an aroma, an incense, a flavouring and / or a pharmaceutical composition. Also provided in a fragrance, an aroma, an incense, a flavouring and / or a pharmaceutical composition comprising an oxidised sesquiterpene produced according to the process described herein. The fragrance, an aroma, an incense, a flavouring and / or a pharmaceutical composition may comprise one or more additional agents. For example, the pharmaceutical composition may comprise a pharmaceutically acceptable excipient, carrier, diluent, buffer, stabiliser or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The pharmaceutical carrier or diluent may be, for example, an isotonic solution. The precise nature of the carrier or other material may depend on the route of administration, e.g. oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular and intraperitoneal routes. For example, solid oral forms may contain, together with the active substance, diluents, e.g. lactose, dextrose, saccharose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and / or polyethylene glycols; binding agents; e.g. starches, gum arabic, gelatin, methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; disaggregating agents, e.g. starch, alginic acid, alginates or sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and, in general, non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. Such pharmaceutical preparations may be manufactured in known manner, for example, by means of mixing, granulating, tabletting, sugar-coating, or film-coating processes. Oral formulations include such normally employed excipients as, for example, pharmaceutical grade mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain 10% to 95% of active ingredient, preferably 25% to 70%. Where the pharmaceutical composition is lyophilised, the lyophilised material may be reconstituted prior to administration, e.g. a suspension. Reconstitution is preferably effected in buffer. Capsules, tablets and pills for oral administration to an individual may be provided with an enteric coating comprising, for example, Eudragit “S”, Eudragit “L”, cellulose acetate, cellulose acetate phthalate or hydroxypropylmethyl cellulose. Liquid dispersions for oral administration may be syrups, emulsions or suspensions. The syrups may contain as carriers, for example, saccharose or saccharose with glycerine and / or mannitol and / or sorbitol. Suspensions and emulsions may contain as carrier, for example a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose, or polyvinyl alcohol. The suspensions or solutions for intramuscular injections may contain, together with the active substance, a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol, and if desired, a suitable amount of lidocaine hydrochloride. Solutions for intravenous administration or infusion may contain as carrier, for example, sterile water or preferably they may be in the form of sterile, aqueous, isotonic saline solutions. For suppositories, traditional binders and carriers may include, for example, polyalkylene glycols or triglycerides; such suppositories may be formed from mixtures containing the active ingredient in the range of 0.5% to 10%, preferably 1% to 2%. Administration may be in a "prophylactically effective amount" or a "therapeutically effective amount" (as the case may be, although prophylaxis may be considered therapy), this being sufficient to show benefit to the individual, e.g. an effective amount to prevent or delay onset of a disease or condition, to ameliorate one or more symptoms, to induce or prolong remission, or to delay relapse or recurrence. The invention also relates to a polynucleotide which comprises a sequence which encodes the mutant CYP102A enzyme of the invention. The polynucleotide may be in the form of a vector. The vector is typically a transposon, plasmid, virus or phage vector. It typically comprises an origin of replication. It typically comprises one or more selectable marker genes, for example an ampicillin resistance gene in the case of a bacterial plasmid. The vector is typically introduced into host cells using conventional techniques including calcium phosphate precipitation, DEAE- dextran transfection, or electroporation. The invention also relates to a cell that expresses the mutant CYP102A enzyme of the invention. The cell may be a prokaryotic cell. The cell may be a eukaryotic cell. The cell may be a strain of bacteria such as Escherichia coli, Pseudomonas sp., Rhodococcus sp. or Bacillus sp. The cell may be a strain of yeast, such as Pichia sp. The invention also relates to a transgenic animal or plant that comprises cells that express the mutant CYP102A enzyme of the invention. The transgenic animal may be a non- mammalian animal, such as a non-human animal. The animal or plant is transgenic for one or more polynucleotides encoding the mutant CYP102A enzyme. They may be homozygotic or heterozygotic for such polynucleotides, which are typically transiently introduced into the cells, or stably integrated. The plant or animal may be obtained by transforming an appropriate cell (e.g. embryo stem cell, callus or germ cell), fertilizing the cell if required, allowing the cell to develop into the animal or plant and breeding the animal or plant if required. The animal or plant may be obtained by sexual or asexual reproduction (e.g. cloning), propagation of an animal or plant of the invention or of the F1 organism (or any generation removed from the F1, or the chimera that develops from the transformed cell). The cell is typically produced by introducing into a cell (i.e. transforming the cell with) the vector comprising a polynucleotide that encodes the mutant CYP102A enzyme of the invention. It is to be understood that due to the degeneracy of the nucleotide code, more than one polynucleotide can encode each of the mutant CYP102A enzymes. It is also to be understood that the nucleotide sequence may be engineered to exhibit a codon bias suitable for a particular cell or organism. The vector may integrate into the genome of the cell or remain extra-chromosomal. The cell may develop into the animal or plant. Typically the coding sequence of the polynucleotide is operably linked to a control sequence which is capable of providing for the expression of the coding sequence by the host cell. The control sequence is generally a promoter, typically of the cell in which the monooxygenase is expressed. The term "operably linked" refers to a juxtaposition wherein the components described are in a relationship permitting them to function in their intended manner. A control sequence "operably linked" to a coding sequence is ligated in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequences. The processes disclosed herein may be performed in the cell expressing the mutant CYP102A enzyme. The process may be performed in vitro, such as in culture, in vivo or in planta. Uses The invention also provides the use of one or more mutant CYP102A enzymes as described herein for oxidizing a sesquiterpene comprising fused 5- and 7-membered rings. The mutant CYP102A enzymes may be the mutant CYP102A enzymes described herein. The sesquiterpene comprising fused 5- and 7-membered rings may be any of the substrates described herein. The use may be for oxidizing the sesquiterpene comprising fused 5- and 7- membered rings to any of the products described herein, for example for specifically oxidizing the sesquiterpene comprising fused 5- and 7-membered rings to any of the products described herein. Organic compounds Using the process of the invention, the inventors have also obtained a process to obtain the aroma compounds. Accordingly, provided herein are the organic compounds produced using the mutant CYP102A enzymes of the invention, or according to the processes of the invention. The organic compounds may be the δ-guaiene (α-bulnesene) oxidation products disclosed in any of Figures 1 to 3. Preferably, the organic compounds are selected from products 1, 2, 3, 5, 6, 7, 8, 9, 9a and 10 in Figure 2, e.g. δ-guaiene-15-ol, δ-guaiene-15- al, δ-guaiene-15-oic acid, δ-guaiene-2S-ol, δ-guaiene-2R-ol, δ-guaiene-11,12-epoxy-15-ol, δ- guaiene-11,12-epoxy-15-oic acid, δ-guaiene-2-ol-15-oic acid and δ-guaiene-15,2-olide. As described herein, the terms δ-guaiene, bulnesene and α-bulnesene are used interchangeably. The suffix -15,2-olide is used interchangeably with -15,2-lactone. Examples Example 1. Design and engineering of CYP102A1 for the oxidation of α-bulnesene To the best of the inventors’ knowledge, there are no reports of enzymatic synthesis of α-bulnesene-derived compounds which are agarwood aroma components, and no previous literature on P450BM3engineering provided any teaching on how to design mutations to impart selective oxidation of α-bulnesene to the C15-alcohol precursor to agarwood aroma compounds. A designed-library approach was adopted whereby an initial screening library of 48 P450BM3variants were constructed from five base variants, K19 (H171L / Q307H / N319Y), RT2 (R47L / Y51F / A191T / N239H / I259V / A276T / L353I), RP (R47L / Y51F / I401P), R19 (R47L / Y51F / K19), and GVQ (A74G / F87V / L188Q) (Whitehouse, et al., Chem. Commun. 2008, 44, 966–968). Different combinations of mutations of substrate pocket residues were added to these base variants to generate a panel of enzymes with diverse substrate pocket topologies to obtain matches with the size and shape of unnatural substrates for their binding and oxidation. Screening reactions (0.5 mL) were conducted in 24-well plates with 2 mM bulnesene substrate and 2 μM P450BM3enzyme (0.1% catalyst) using a cyclodextrin to increase the aqueous solubility of the substrate; glucose and glucose-dehydrogenase were used to regenerate the NADPH cofactor. After shaking for 6 hours, the reaction mixture in each well was extracted with ethyl acetate and the extract was analysed by gas chromatography (GC). The results showed that 26 out the 48 variants in the library possessed >50% bulnesene conversion activity (total turnover number, TON, >500). Active variants were selected for preparative scale reactions, from which five bulnesene oxidation products were isolated and characterised by their NMR and MS data as 15-hydroxy-bulnesene (bulnesene-15-ol, 1), the aldehyde bulnesene-15-al (2), (2S)-hydroxy- bulnesene (6), (2R)-hydroxy-bulnesene (7), and 15-hydroxy-11,12-epoxy-bulnesene-15-ol (8) (which was likely to be the further oxidation product of 1 (Figure 2)). The other products were either not formed with sufficient selectivity or could not be isolated in sufficient quantities for characterisation. The activity profile of the library of 48 P450BM3variants showed that variants with the F87A and F87V mutations commonly utilised to promote the oxidation of unnatural substrates by P450BM3(Whitehouse, et al., Chem. Soc. Rev.2012, 41, 1218–1260), showed high conversion but low selectivity, with numerous products being formed. Variants with the A330P mutation, which reduced the volume of the substrate pocket in the vicinity of the heme (Whitehouse, et al., ChemBioChem 2010, 11, 2549–2556), showed little bulnesene conversion. Five variants from this initial library showed >60% total products arising from C15 oxidation (Table 1, Entries 1–5), revealing the combination of mutations A82M, F87I, A184I and T260G to be important in promoting C15 oxidation of bulnesene. The R19 / F87I variant showed the highest conversion (100%) and the highest selectivity (51%) for the C15- aldehyde 2 (Entry 1). The R19 / A82M / T260G and R19 / A184I / T260G variants showed >60% selectivity for the C15 alcohol 1, with no further oxidation to the aldehyde, but with lower TONs (Entries 4 and 5). Table 1. Activity and product selectivity (GC) for the oxidation of α-bulnesene catalysed by selected cytochrome P450BM3variants. The substrate / enzyme concentration ratio was 1000:1 (2 mM bulnesene and 2 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products. C15 is the total percentage of products from oxidation at C15. TON is the turnover number of the variant for the formation of C15-alcohol (1), C15- aldehyde (2), and C15-carboxylic acid (3). K19=H171L / Q307H / N319Y; R19=R47L / Y51F / K19. Numbering 1, 2, 3, 6, 7 and 8 refer to products shown in Figure 2. Entry P450BM3variant Conv. 1 2 3 6 7 8 C15 TON 1 R19 F87I 100% 15% 51% 15% – – 6% 81% 810 2 K19 F87I 79% 52% 18% – 4% – 6% 70% 555 3 R19 A82M A184I T260G 93% 54% 14% – – – 6% 68% 635 4 R19 A82M T260G 69% 66% – – 6% – – 66% 455 5 R19 A184I T260G 80% 63% – – 3% 7% 7% 63% 505 6 R19 F87I A82M 86% – 7% 70% – – – 77% 665 7 R19 F87I A184I 91% – 3% 72% – – – 75% 685 8 R19 F87I T260G 33% 72% – – – – – 72% 240 In the next step of enzyme engineering for bulnesene oxidation, new variants were generated by adding the mutations A82M, A184I and T260G to the R19 / F87I variant. With the addition of either the A82M or A184I mutation, C15 alcohol 1 was not observed but a new product with a longer GC retention time was formed with >70% selectivity. This compound was isolated from preparative scale reactions and characterised as the C15 carboxylic acid bulnesene-15-COOH, 3. The results suggested that addition of mutations A82M and A184I had increased enzymatic activity and further oxidation of C15 alcohol 1 to aldehyde 2 was followed by oxidation to acid 3, with high selectivity (>70%) and good conversion (>85%) (Entries 6 and 7). On the other hand, the R19 / F87I / T260G variant showed lower conversion (33%) but high selectivity for 15-alcohol 1, demonstrating that the T260G mutation could be crucial in hindering further oxidation of 1 to aldehyde 2 (Entry 8). Example 2. Second generation variants Bulnesene, bulnesene-15-ol (1) and bulnesene-15-aldehyde (2) were computationally docked into the molecular dynamics (MD) simulation structure of the R19 / F87I variant to explore the enzyme–substrate interactions that led to a hydrocarbon being oxidised to the alcohol, then the aldehyde and eventually the carboxylic acid. The substrate binding poses were divided into two categories – productive poses with carbon centre(s) within 4 Å of the ferryl oxygen for oxidation and non-productive poses in which no substrate carbon centre is within 4 Å of the ferryl oxygen. The poses indicating C15 oxidation were overlaid with the non-productive poses and poses that led to oxidation at other carbon positions. Residues that were in van der Waals contact or formed hydrogen bonds (to the alcohol and aldehyde groups) with these non-productive and undesired poses were targeted for mutagenesis by substituting them with residues with bulkier hydrophobic side chains. Such side chains could destabilise the undesired and non-productive poses without affecting the desired ones, thus increasing the activity and selectivity for C15 oxidation of bulnesene. Such mutations were introduced at 16 residues: V26, L71, S72, A74, L75, T88, L181, T260, I263, A264, A328, A330, S332, K434, L437 and T438. Selected activity and selectivity data are summarised in Table 2. Most of the introduced mutations did not promote bulnesene oxidation except for mutations of residues V26, L71, T88 and A330 (Table 2). The variants with high selectivity for C15-alcohol 1 showed lower conversion in general. The L71M mutation promoted the formation of acid 3 (from 14% to 20%, Table 2, Entry 11) while maintaining the total C15 selectivity (79%). Mutations at T88 increased the total C15 selectivity to 90%. For example, the R19 / F87I / T88F variant gave bulnesene-15-ol 1 as the major product (65%) and showed the highest TON (835) of the new variants (Entry 13). Residue A330 was found to play a crucial role in the oxidation of bulnesene. By substituting alanine (A) with valine (V) or isoleucine (I), the selectivity of C15-acid 3 was increased; the highest was observed with R19 / F87I / A330V which gave 30% of 3 with 85% total C15 selectivity and a total TON for C15 oxidation of 800 (Entry 15). The mutations which showed increased activity, including V26L / M, A82M, A184I and A330I / V, were then combined with the aim to improve the bulnesene oxidation activity. Despite showing enhanced activity when added separately, the combination A82M / A184I decreased activity (Entry 26). However, when mutations A330I or A330V were added to R19 / F87I / A82M and R19 / F87I / A184I, the overall C15 selectivity increased for all the new variants. R19 / F87I / A82M with A330I / V gave similar products compared to the precursor R19 / F87I / A82M but at lower TON (Entries 6, 24 and 25). Table 2. Activity and product selectivity (GC analysis) for the hydroxylation of α-bulnesene catalysed by selected cytochrome P450BM3variants. The substrate / enzyme ratio was 1000:1 (2 mM bulnesene, 2 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products. C15 is the total selectivity for C15 oxidation to form C15-alcohol 1, C15-aldehyde 2, and C15-carboxylic acid 3. TON is the turnover number of the variant for C15 oxidation.a6% of the 2R-alcohol 7 was also formed. Entry P450BM3 variant Conv. 1 2 3 9 9a C15 TON 9 R19 F87I V26L 92% 16% 48% 10% – – 74% 685 10 R19 F87I V26M 93% 20% 46% 10% – – 76% 710 11 R19 F87I L71M 94% 16% 44% 20% – – 79% 745 12 R19 F87I T88L 85% 55% 25% – – – 80% 680 13 R19 F87I T88F 93% 65% 25% – – – 90% 840 14 R19 F87I T88M 96% 21% 31% 17% – – 69% 665 15 R19 F87I A330V 93% 10% 45% 30% – – 85% 795 16 R19 F87I A330I 90% 11% 45% 26% – – 82% 740 17 R19 F87I A330F 87% 12% 13% 24% 5% – 49% 430 18 R19 F87I A330W 75% 30% 19% 16% – – 64% 480 19 R19 F87I A330Pa89% 17% 19% 11% – – 47% 420 20 R19 F87I A184I 98% – – 70% 6% 3% 70% 690 V26L 21 R19 F87I A184I 96% – 4% 72% – – 76% 730 V26M 22 R19 F87I A184I 76% 11% 13% 57% – 4% 81% 620 A330I 23 R19 F87I A184I 94% – 3% 78% 6% 6% 81% 765 A330V 24 R19 F87I A82M 71% 4% 7% 69% – 11% 80% 570 A330I 25 R19 F87I A82M 83% 4% 7% 68% – – 79% 660 A330V 26 R19 F87I A82M 83% 33% 19% 30% – 10% 82% 685 A184I 27 R19 F87I A82M 82% – – 31% – 49% 31% 255 A330I A184I 28 R19 F87I A82M 93% 7% 6% 42% – 34% 55% 515 A330V A184I 29 R19 F87I A82M 87% – 5% 58% – 19% 63% 550 A330I V26L 30 R19 F87I A82M 90% – 7% 57% – 17% 64% 580 A330V V26L 31 R19 F87I A82M 85% – 9% 62% – 12% 71% 605 A330I V26M Table 3. Activity and product selectivity (GC analysis) for the hydroxylation of α-bulnesene catalysed by selected cytochrome P450BM3variants. The substrate / enzyme ratio was 1000:1 (2 mM bulnesene, 2 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products (C15-alcohol 1, C15-aldehyde 2, C15-carboxylic acid 3, (2S)-alcohol 6 and (2R)-alcohol 7). –: not observed. RP = R47L / Y51F / I401P; RT2 = R47L / Y51F / A191T / N239H / I259V / A276T / L353I; R19 = R47L / Y51F / H171L / Q307H / N319Y. Entry P450BM3 variant Conv. 1 2 3 6 7 Other 61 R19 F87I S72V 60% 70% 6% – 9% – 15% 62 R19 F87I S72I 84% 53% 17% – 10% – 20% 63 R19 F87I S72L 76% 61% 13% – 10% 4% 12% 64 R19 F87I A74L 91% 31% 43% 5% – – 21% 65 R19 F87I A82I 86% 14% 32% 35% – – 19% 66 R19 F87I L181F 84% 18% 30% 21% – – 31% 67 R19 F87I T260L 81% 44% 30% – – – 26% 68 R19 F87I A184I S72L 95% 28% 52% 12% – – 8% 69 R19 F87A A328I 100% 29% 8% 4% 34% – 25% 70 R19 F87A A328I S72A 96% 20% 12% – – 19% 49% 71 R19 F87A A328I S72W 55% 39% 7% – 4% 28% 22% 72 R19 F87A A328I V78I 90% 56% 7% – – 32% – 73 A74G F87L L188Q I263G 75% 42% – – 21% 13% 24% 74 RP I263A E267V 34% 20% – – 16% 4% 60% 75 RP V78I E267V 97% 7% 34% – 2% – 57% 76 RT2 S72G A330W 84% 20% – – 14% 10% 56% 77 RT2 S72W A330W 64% 21% – – 14% 10% 55% Table 4. Activity and product selectivity (GC analysis) for the hydroxylation of α-bulnesene catalysed by selected cytochrome P450BM3variants. The substrate / enzyme ratio was 1000:1 (2 mM bulnesene, 2 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products (C15-alcohol 1, C15-aldehyde 2, C15-carboxylic acid 3, 15,2-lactone 5, the 11,12-epoxides of the C15-carboxylic acid 9+9a). –: not observed. R19 = R47L / Y51F / H171L / Q307H / N319Y. Entry P450BM3variant Conv. 1 2 3 5 9+9a Other 78 R19 F87I A82M 94% 4% 6% 69% 2% 12% 7% A330I A184I L71F 79 R19 F87I A82M 98% 3% 2% 31% 3% 55% 6% A330I A184I L71M 80 R19 F87I A82M 97% 2% – 36% 5% 43% 14% L171H A330I A184I V178F 81 R19 F87I A82M 96% – – 5% 2% 79% 14% A330I A184I S332M V78A 82 R19 F87I A82M 80% – – 17% 2% 60% 21% A330I A184I L437V 83 R19 F87I A82M 95% 4% 5% – 2% 63% 26% A330I A184I L437M Table 5. Activity and product selectivity (GC analysis) for the hydroxylation of α-bulnesene to (2S)-alcohol 6 and (2R)-alcohol 7 catalysed by selected cytochrome P450BM3variants. The substrate / enzyme ratio was 1000:1 (2 mM bulnesene, 2 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products. RP = R47L / Y51F / I401P; KU3 = N239H / A276T / L353I; R19 = R47L / Y51F / H171L / Q307H / N319Y; RT2 = R47L / Y51F / A191T / N239H / I259V / A276T / L353I. Entry P450BM3 variant Conv. 6+7 Other84 R19 F87A A328L 100% 37% 63%85 R19 F87A A328I A264G 99% 35% 65%86 R19 F87A A328I V78I 90% 32% 68%87 R19 F87A A328I S72W 55% 32% 68%88 R19 A328L A184I 58% 29% 71%89 R19 A330W 35% 52% 48%90 R19 P329G A330W 51% 55% 45%91 RT2 S72G A330W 84% 47% 53%92 KU3 A330P 55% 53% 47%93 RP A82M A330W 39% 47% 53%94 RP A82M A330W I263A 49% 45% 55%95 RP H171L I263G A82M 61% 57% 43%96 RP H171L I263G S72W 61% 22% 78%97 RP F87V V78I 35% 41% 59%98 A74G F87V L188Q A264G 62% 37% 63%99 A74G F87L L188Q I263G 75% 34% 66%100 A74G F87L L188Q I263G A328F 93% 31% 69% The R19 / F87I / A82M / A330I variant also gave a new product with a longer retention time than 3; this product was isolated from a preparative scale reaction and characterised as 11,12-epoxy-bulnesene-15-COOH (9a) – the epoxidation product of acid 3. Variant R19 / F87I / A184I / A330V showed increased selectivity for 3 (78%) and with high conversion (94%, Entry 23). On the other hand, the A330I mutation lowered the selectivity for 3 to 57% and reduced conversion to 76% (Entry 22). The combination of A184I with V26L / M also promoted the formation of acid 3 but with lower total C15 selectivity (70% and 76%, Entries 20 and 21). Some variants also promoted the formation of the other isomer of 11,12-epoxy- bulnesene-15-COOH (9) (Table 2, Entries 17, 20 and 23). The isomeric epoxides 9 and 9a differed in the absolute configuration at C11 but no assignment was possible due to lack of literature data for comparison. Combinations of mutations at A184 and A330, or at V26, A82M and A330, led to further oxidation of acid 3 to 11,12-epoxy-bulnesene-15-COOH (9a) (Table 2, Entries 27–31). The highest selectivity for 9a (49%) was observed with the variant R19 / F87I / A82M / A330I / A184I (Entry 27). All the variants were tested again at a higher bulnesene / enzyme ratio of 8000:1 (8 mM bulnesene and 1 µM P450BM3enzyme). R19 / F87I gave reasonable conversion (62%) with high selectivity (70%) for bulnesene-15-ol 1 (Table 6, Entry 32). On the other hand, R19 / F87I / V26M / A82M / A330I and R19 / F87I / A82M / A184I / A330I gave high selectivity for bulnesene-15-al 2 (47% and 41% respectively) and high total C15 selectivity (92% and 91% respectively). The highest TON of 5,600 was observed with the R19 / F87I / V26M / A82M / A330I variant (Entry 33). Table 6. Titre test, activity and product selectivity (GC analysis) for the hydroxylation of α- bulnesene catalysed by selected cytochrome P450BM3variants. The substrate / enzyme ratio was 8000:1 (8 mM bulnesene, 1 μM P450BM3enzyme). Conv. is the percentage of the bulnesene substrate converted to products. C15 is the total selectivity for C15 oxidation to form C15-alcohol 1, C15-aldehyde 2, and C15-carboxylic acid 3. TON is the turnover number of the variant for C15 oxidation.Entry P450BM3 variant Conv. 1 2 3 C15 TON32 R19 F87I 62% 70% 16% – 86% 426033 R19 F87I V26M A82M A330I 76% 39% 47% 6% 92% 5600R19 F87I A82M A184I A330I L171H 3489% 38% 40% 17% 95% 6770V178F In summary, screening of a designed library of just 48 P450BM3enzyme variants followed by combining beneficial mutations for enzymatic activity and product selectivity led to variants with high selectivity for the formation of the C15-alcohol 1, the C15-aldehyde 2, and the C15-acid 3. Computational substrate docking followed by the introduction of mutations to disfavour binding poses indicating unwanted products or non-productive poses, further tuned the complementarity between the active site pocket and the substrate to increase activity and selectivity. C15-aldehyde 2 is a desirable agarwood aroma compound, and the C15-alcohol precursor 1 may have applications as a novel aroma. The engineered P450BM3variants offer enzymatic routes for the synthesis of both compounds. R19 / F87I is an excellent candidate for the biocatalytic synthesis of 1, with the highest selectivity (70% of 1) and good conversion (62%) and TON (4,260) at a bulnesene / enzyme ratio of 8000:1 (Table 6, Entry 32). The synthesis of 2 via bulnesene oxidation requires the catalyst to form alcohol 1 and then aldehyde 2 with minimal further oxidation to form acid 3. This chemoselectivity is more challenging to achieve. For example, the R19 / F87I and some other variants (Tables 1 & 2) give 40–50% of 2 at 1000:1 ratio but there is further oxidation to acid 3 whereas other variants give less of 2 and 3 but more of 1. The R19 / F87I / V26M / A82M / A330I variant showed 76% bulnesene conversion to 39% of 1 and 47% of 2 but very little acid (6%) at 8000:1 ratio. The high total C15 selectivity (92%) and TON (5,600) (Table 6, Entry 33) make this variant an excellent candidate for a process which oxidises bulnesene to a mixture of 1 and 2, followed by selective chemical or enzymatic oxidation of 1 to give 2, leading to high selectivity for the formation of aldehyde 2. The highest total C15 selectivity (95%) and TON (6,770) are observed with the R19 / F87I / A82M / A184I / A330I / L171H / V178F variant (Table 6, Entry 34). Example 3. Synthesis of bulnesene-15,2-lactone by P450BM3-catalysed oxidation of bulnesene Bulnesene-15,2-lactone (5) is a major contributor to the aroma of agarwood. The biosynthetic route to 5 likely proceeds via initial P450-catalysed C15 oxidation to the alcohol 1. The aldehyde 2 may be formed by the action of the same or another P450 enzyme, or a dehydrogenase, and then 2 most likely oxidised to acid 3 by an aldehyde oxidase. The acid is then hydroxylated at C2 to form 2-hydroxy-bulnesene-15-COOH, 4, which cyclises to lactone 5. The surprising discovery via docking-guided mutagenesis of P450BM3variants that oxidised bulnesene directly to acid 3 with high selectivity and conversion, provided new routes. Firstly, these P450BM3variants can be further engineered to oxidise acid 3 at C2 to form 4, the precursor to lactone 5. Alternatively, another P450BM3variant is engineered to oxidise acid 3 at C2. Two P450BM3enzyme variants are then combined in an enzymatic cascade in a one-pot reaction in which bulnesene is oxidised to the acid 3 by one variant while the other variant oxidises the acid to the C2 alcohol 4. It is desirable for the second enzyme to have little activity for bulnesene oxidation at positions other than C15 while the first enzyme in the cascade, if it is active for oxidation of the acid 3, should not oxidise the acid at positions other than C2. Several variants generated from the R19 / F87I template (Tables 1 & 2) were utilised to oxidise bulnesene to acid 3 which was then purified for use as the substrate for screening of the P450BM3variant library for oxidation activity. Screening reactions were carried out at an acid / P450BM3ratio of 500:1 (1 mM of acid 3 and 2 µM of P450BM3). The reaction mixtures were treated with 100 μL of 2 M HCl for 1 hour at 40 °C to promote formation of lactone 5 from any 2-hydroxy-bulnesene-15-COOH (4) formed and then extracted with ethyl acetate for GC analysis of the organics. The screening panel of 48 enzymes was less active for the oxidation of acid 3 compared to bulnesene. Only eight variants gave conversion higher than 40% after 16 hours. These were mostly based on the template variants K19 / F87V, KT2, KU3 / A330P and R19 / F87A, and the epoxides 9 and 9a were the major products; for example, the variants R19 / F87A / A184I (Table 7, Entry 35) and R19 / F87A / I263G (Entry 36) gave 65–70% of 9 and 9a in total. A new product was observed with variants containing the I263G mutation, for example, 6% with the R19 / F87A / I263G variant (Entry 36), while the A330P mutation disfavoured formation of epoxides 9 and 9a. A new set of P450BM3variants was then generated by introducing mutations at the I- helix residues I263 and A264, and the β4strand residues A328 and A330, to the R19 / F87A / A184I variant. The I263G, A264G, A328G and A330P mutations increased conversion and altered the product profiles (Table 7). The R19 / F87A / A184I / I263G / A264G / A328G (Table 7, Entry 40) variant gave 55% of the new product observed with R19 / F87A / I263G. This new product was isolated and characterised as the 15,2-lactone 5 by its NMR and MS data. The oxidation site had changed from mainly epoxidation of the C11=C12 double bond to hydroxylation at C2 and other carbons. Variants with A328G and A330P showed lower selectivity for epoxides 9 and 9a which demonstrated the importance of A330P and A328G in changing the binding orientation of the C15-acid 3 in the substrate pocket (Table 7, Entries 37–42). Mutation A330P also increased conversion; acid 3 was almost fully converted by the R19 / F87A / A184I / A330P (Entry 37) and R19 / F87A / A184I / I263G / A330P (Entry 41) variants in 16 hours. Table 7. Activity and product selectivity (GC) for the oxidation of bulnesene-15-COOH 3 catalysed by selected cytochrome P450BM3variants. The substrate / enzyme concentration ratio was 500:1 (1 mM bulnesene and 2 μM P450BM3enzyme). Conv. is the percentage of the substrate converted to products. TON is the turnover number of the variant for the formation of lactone 5. Entry P450BM3 variant Conv. 9 9a 5 TON 35 R19 F87A A184I 52% 22% 52% 5% 15 36 R19 F87A I263G 83% 20% 47% 6% 25 37 R19 F87A A184I A330P 97% 9% 21% – – 38 R19 F87A A184I I263G A264G 53% 1% 41% 14% 40 39 R19 F87A A184I I263G A328G 42% 5% 19% 15% 35 40 R19 F87A A184I I263G A264G A328G 98% – 9% 55% 270 41 R19 F87A A184I I263G A330P 98% 10% 26% 19% 9542 R19 F87A A184I I263G A264G A330P 100% 6% 14% 61% 305 Another round of mutagenesis was conducted to add the A330P mutation to variants that formed the 15,2-lactone to increase the conversion and selectivity for this target product. One new variant, R19 / F87A / A184I / I263G / A264G / A330P, increased the conversion of acid 3 to 100% compared to 98% by R19 / F87A / A184I / I264G / A264G / A328G and with higher selectivity for 15,2-lactone 5 at 61% (Table 7, Entries 40 and 42). However, the expression levels of both variants were poor. New variants with higher expression levels and selectivity for the 15,2-lactone were needed. Further mutagenesis based on the variants listed in Table 7 would be challenging because of the poor expression levels of the enzymes. Therefore, instead of adding mutations to these variants or replacing existing mutations, the effect of each constituent mutation was studied by sequential addition of these mutations and monitoring the effect on the expression level and the activity and selectivity for the 15,2-lactone. Mutations F87A, A184I, I263G, A264G, A328G and A330P were the main targets in this round of mutagenesis. Table 8. Activity and product selectivity (GC analysis) for the hydroxylation of bulnesene- 15-COOH 3 catalysed by selected cytochrome P450BM3variants. The substrate / enzyme concentration ratio was 500:1 (1 mM bulnesene and 2 μM P450BM3enzyme). Conv. is the percentage of the substrate converted to products. TON is the turnover number of the variant for the formation of the 15,2-lactone 5. Entry P450BM3 variant Conv. 9 9a 5 TON 43 F87A I263G 37% 30% 47% – – 44 F87A A330P – – – – – 45 F87A I263G A264G 12% 14% 41% – – 46 F87A I263G A330P 100% 31% 25% 5% 25 47 F87A A184I A330P 76% 24% 39% – – 48 F87A A184I I263G A330P 100% 17% 28% 10% 50 49 F87A A184I I263G A264G A328G 51% 4% 11% 51% 13050 F87A A184I I263G A264G A330P 100% 6% 14% 65% 325 The results (Table 8) indicated that the appropriate combinations of mutations were required for activity. Whereas the F87A / I263G variant (Table 8, Entry 43) showed some conversion of acid 3 to the epoxides 9 and 9a (but not the 15,2-lactone), the F87A / A330P variant (Entry 44) was inactive towards 3. On the other hand, addition of the A184I mutation raised the conversion of the F87A / A330P variant to 76% (Entry 47) although the major products remained the epoxides 9 and 9a. The first appearance of the 15,2-lactone (5%) was found with the F87A / I263G / A330P variant which showed high conversion (100%, Entry 46). Addition of the A184I mutation raised the lactone selectivity to 10% for the F87A / A184I / I263G / A330P variant (Entry 48). Previous results showed the importance of the combination of A184I / I263G / A264G and A184I / I263G / A330P in increasing conversion and biasing the product selectivity towards lactone 5 (Entries 38 and 41). When these mutations were combined, the variant F87A / A184I / I263G / A264G / A330P gave 65% of the 15,2-lactone with full conversion (Entry 50). Hence, lactone selectivity was increased while maintaining expression levels compared to the best variant from the previous generation (R19 / F87A / A184I / I263G / A264G / A330P). Another important property of the F87A / A184I / I263G / A264G / A330P variant was its low activity for bulnesene oxidation, which made it an excellent candidate for the second enzyme (to convert the acid 3 to the lactone 5) in the proposed P450BM3enzyme cascade. Example 4. A single P450BM3enzyme variant for direct oxidation of bulnesene to the 15,2- lactone The variant R19 / F87I / A82M / A184I / A330I oxidised bulnesene with high activity, firstly to the C15-acid 3, then to the 11,12-epoxides 9 / 9a (Table 2, Entry 27). It also gave the 15,2-lactone 5 as a minor product (4%). Therefore, this variant was selected for mutagenesis with the aim of switching the selectivity for the oxidation of C15-acid 3 from epoxidation of the C11=C12 double bond to C2 hydroxylation. Acid 3 was computationally docked into the active site of molecular dynamics simulation structures of the R19 / F87I / A82M / A184I / A330I variant. Residues that were in van der Waals contact or formed hydrogen bonds with the poses indicating epoxidation were targeted for mutagenesis to disfavour such poses, and mutations were introduced at eight residues: L71, S72, A74, L75, V78, L188, S332 and L437. The 15,2-lactone 5 was formed for the R19 / F87I / A82M / A184I / A330I / V78A / S332M variant, with 19% selectivity; the major product was the epoxide 9a, as found for the precursor variant. Since the selectivity for the 15,2-lactone remained low after so many residues had been subjected to mutagenesis, it appeared that it would be preferable to utilise a one-pot cascade enzyme system in which one enzyme (such as the R19 / F87I / A82M / A184I / A330I variant) generated the acid 3 with high conversion and selectivity while a second enzyme (such as the F87A / A184I / I263G / A264G / A330P variant which has little activity for bulnesene oxidation) converted acid 3 to 4, the precursor to lactone 5. Example 5. A cascade of P450BM3enzyme variants for the synthesis of bulnesene-15,2- lactone, 5 In the cascade approach, a P450BM3variant enzyme (E1) catalyses three cycles of oxidation of bulnesene at C15 to form acid 3 which is then oxidised at the C2 position by a second P450BM3variant enzyme (E2) in a one-pot reaction. As E1 would compete with E2 in oxidising the acid 3, for example, to the epoxides 9 and 9a, the reaction conditions have to be optimised by changing the variant to be used as E1, the E1 / E2 ratio, and the bulnesene / enzyme ratio. Two variants, R19 / F87I / A82M and R19 / F87I / A82M / A330V, which oxidised bulnesene to acid 3 with high selectivity, were selected as candidates for E1. These were used with different concentrations of E2 (F87A / A184I / I263G / A264G / A330P) to determine the optimum conditions for the cascade reaction. Table 9. Bulnesene conversion and the relative amounts of 15,2-lactone 5 formed by cascades of different P450BM3variants E1 and the F87A / A184I / I263G / A264G / A330P functioning as E2. The bulnesene / E1 ratio was 1000:1 (2 mM bulnesene and 2 μM of each of the P450BM3enzymes). The reaction time was 6 hours. The concentrations of bulnesene and its metabolites were expressed as the ratio of the peak area of each compound to the peak area of an added internal standard. E1:E2 Entry E1 variant ratio Bulnesene Aldehyde 2 Acid 3 Lactone 5 51 R19 F87I 1:1 0.07 0.27 0.99 1.76 52 A82M 1:1.5 – 0.08 0.49 1.96 53 1:2 – – 0.17 2.01 54 1:2.5 – – 0.09 2.13 55 1:3 – – – 2.35 56 R19 F87I 1:1 0.10 0.11 1.24 2.24 57 A82M A330V 1:1.5 0.07 – 0.27 2.42 58 1:2 0.05 – – 2.31 59 1:2.5 – – – 2.31 60 1:3 0.06 – – 2.09 Both E1 variants showed good bulnesene conversion in 6 hours (Table 6). Generally, higher conversion of 15-COOH 3 was achieved as the amount of E2 increased. The amount of lactone 5 grew as the E1:E2 ratio was increased for variant R19 / F87I / A82M while the highest lactone formation was achieved with 1:1.5 ratio for variant R19 / F87I / A82M / A330V (Table 9, Entry 57). The C15 oxidation products of bulnesene formed by engineered variants of P450BM3and conversion of the C15-acid to the 2-hydroxy derivative and the 15,2-lactone are summarised in Figure 3 together with the control of products formed by variation of the enzyme variant and reaction conditions. Example 6. Materials and methods used in Examples 1-5 Screening of bulnesene and bulnesene-15-COOH for oxidation by P450BM3 variants Bulnesene was dissolved in EtOH and added as a 400 mM stock solution. Screening reaction mixtures in 200 mM phosphate buffer (pH 7.9) contained 2 mM bulnesene and 2 μM P450 enzyme in a volume of 0.5 mL in 24-well plates. Glucose (100 mM) and glucose dehydrogenase (4 U mL–1) were used to regenerate the cofactor NADPH from NADP+(4 μM). Methyl-β-cyclodextrin was added to 10 mM to increase the aqueous solubility of bulnesene. Screening pates were shaken at 120 rpm for 6 hours at 20 °C. Organics were extracted with 300 μL ethyl acetate and analysed by GC. The procedure for the screening reactions were similar for the screening of bulnesene-15-COOH 3 at 500:1 ratio (1 mM acid 3 and 2 μM P450 enzyme) for 24 hours but the mixtures were acidified with 100 μL of 2 M HCl. 400 µL of the mixture was extracted with 300 µL ethyl acetate and the organics were analysed by GC. Screening scale one-pot cascade oxidation of bulnesene to the 15,2-lactone Bulnesene was dissolved in EtOH and added as a 400 mM stock solution to a final concentration of 2 mM to reactions with 2 µM of enzyme E1 and 4 μM of enzyme E2 in a volume of 0.5 mL in 24-well plates. Glucose (100 mM) and glucose dehydrogenase (4 U mL–1) were used to regenerate the cofactor NADPH from NADP+(4 μM). Methyl-β-cyclodextrin was added to 10 mM to increase the solubility of bulnesene in 200 mM phosphate buffer, pH 7.9. Screening pates were shaken at 120 rpm for 24 hours at 20 °C, 100 μL of 2 M HCl was added to each reaction mixture which was heated at 40 °C for one hour. 400 µL of the mixture was extracted with 300 µL ethyl acetate and analysed by GC. Preparative scale oxidation of bulnesene for 15,2-lactone synthesis The scalability of the synthesis of the 15,2-lactone of bulnesene via oxidation of bulnesene by a cascade of engineered P450BM3variants was illustrated by a one-pot reaction utilising R19 / F87I / A82M / A330V and F87A / A184I / I263G / A264G / A330P variants in a ratio of 1:1.5. The reaction was scaled to 200 mL using the same concentrations of each component as for screening scale reactions. The reaction mixture was stirred at ambient temperature for 24 hours. Aliquots were removed periodically to monitor the progress of the reaction by GC, which showed that bulnesene conversion had reached >95% after 24 hours. The reaction mixture was adjusted to pH 1, heated at 40 °C for 4 hours, and then extracted three times with an equal volume of ethyl acetate. The combined extracts were washed with water and brine, dried over Na2(SO4) and the solvent was removed by rotary evaporation. No further purification was required and the 15,2-lactone 5 was isolated in 38% yield (32 mg) based on the amount of bulnesene converted. Further Embodiments Further embodiments of the invention are set out below: 1. A process for oxidising a sesquiterpene comprising fused 5- and 7-membered rings, comprising contacting said sesquiterpene with a mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing oxygenase activity and / or altering product selectivity of the mutant enzyme. 2. The process according to embodiment 1, wherein the sesquiterpene is a guaiene, a cedrene or a patchoulene. 3. The process according to embodiment 2, wherein the guaiene is δ-guaiene. 4. The process according to embodiment 2 or 3, which is for producing a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. 5. The process according to any one of embodiments 1 to 4, wherein said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2. 6. The process according to any one of embodiments 1 to 5, wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from A82I, A82M, F87I, A184I, A184M, A184F, T260L, T260G, V26L, V26M, L71M, S72V, S72I, S72L, S72A, S72W, A74L, V78I, T88L, T88F, T88M, L181F, I263A, I263G, E267V, A328I, A330V, A330I, A330F, A330P and / or A330W of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme as one or more positions corresponding to the amino acid residues 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2. 7. The process according to any one of embodiments 1 to 6, wherein said mutant CYP102A enzyme comprises one of the following groups of substitutions in SEQ ID NO: 2: i. F87I; v. A82M / A184I / T260G; ii. A82M; vi. F87I / V26L; iii. A82M / T260G; vii. F87I / V26M; iv. A184I / T260G; viii. F87I / L71M; ix. F87I / S72V; xxxii F87I / A184I / A82M; x. F87I / S72I xxxiii. F87I / A184I / A330I; xi. F87I / S72L; xxxiv. F87I / A184I / A330V; xii. F87I / A74L; xxxv. F87I / A82M / A330I; xiii. F87I / A82I; xxxvi. F87I / A82M / A330V; xiv. F87I / A82M; xxxvii. F87I / A82M / A184I; xv. F87I / T88L; xxxviii. F87I / A82M / A330I / A184I; xvi. F87I / T88F; xxxix. F87I / A82M / A330V / A184I; xvii. F87I / T88M; xl. F87I / A82M / A330I / V26L; xviii. F87I / L181F; xli. F87I / A82M / A330V / V26L; xix. F87I / A184F; xlii. F87I / A82M / A330I / V26M; xx. F87I / A184I; xliii. F87A / A328I; xxi. F87I / A184M; xliv. F87A / A328I / S72A; xxii. F87I / T260G; xlv. F87A / A328I / S72W; xxiii. F87I / T260L; xlvi F87A / A328I / V78I; xxiv. F87I / A330V; xlvii. F87L / I263G; xxv. F87I / A330I; xlviii. A184I / A328L; xxvi. F87I / A330F; xlix. E267V; xxvii. F87I / A330W; l. E267V / I263A; xxviii. F87I / A330P; li. E267V / V78I; xxix. F87I / A184I / V26L; lii. A330W; xxx. F87I / A184I / V26M; liii. A330W / S72G; or xxxi. F87I / A184I / S72L; liv. A330W / S72W; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed in i. to liv. 8. The process according to any one of embodiments 5 to 7, wherein the sesquiterpene is a guaiene, and which is for producing a guaiene-15-ol, a guaiene-15-al and / or a guaiene-15- oic acid. 9. The process according to any one of embodiments 1 to 4, wherein said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437. 10. The process according to any one of embodiments 1 to 4 and 9, wherein said mutant CYP102A enzyme comprises substitutions in the polypeptide chain of a wild-type CYP102A enzyme at a position corresponding to amino acid residue position 87 of SEQ ID NO:2, and at one or more positions corresponding to amino acid residue positions 72, 78, 82, 178, 184, 263, 264, 267, 328, 330 and / or 437 of SEQ ID NO: 2. 11. The process according to any one of embodiments 1 to 4, 9 and 10, wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from F87A, F87L, F87V, L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residues 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. 12. The process according to any one of embodiments 1 to 4 and 9 to 11, wherein said mutant CYP102A enzyme comprises a substitution selected from F87A, F87L, F87V, and one or more substitution(s) selected from L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at position 87 and at one or more positions corresponding to the amino acid residues 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2. 13. The process according to any one of embodiments 1 to 4 and 9 to 12, wherein said mutant CYP102A enzyme comprises one of the following groups of substitutions in SEQ ID NO: 2: i. F87A / A184I; xi. F87A / A184I / I263G / A328G; ii. F87A / I263G; xii. F87A / A328I; iii. F87A / A330P; xiii. F87A / A328L; iv. F87A / A184I / A330P xiv F87V / V78I; v. F87A / A184I / I263G / A264G / A328G; xv. F87V / A264G; vi. F87A / A184I / I263G / A330P; xvi. F87I / A82M / A184I / A330I / L71F; vii. F87A / A184I / I263G / A264G / A330P; xvii. F87I / A82M / A184I / A330I / L71M; viii. F87A / I263G / A264G; xviii. F87I / A82M / A184I / A330I / V178F; ix. F87A / I263G / A330P; xix. F87I / A82M / A184I / A330I / V78A / x. F87A / A184I / I263G / A264G; S332M; xx. F87I / A82M / A184I / A330I / L437F; xxvii. I263G / A184I; xxi. F87I / A82M / A184I / A330I / L437M; xxix. I263G / A264G / A328G xxii. F87L / I263G; xxx. E267F xxiii. F87L / I263G / A328F; xxxi. A330P; xxiv. I263G xxxii. A330W; xxv. I263G / S72G; xxxiii. A330W / S72G; xxvi. I263G / S72W; xxxiv. A330W / A82M; or xxvii. I263G / A82M; xxxv. A330W / A82M / I263A; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed in i. to xxxv. 14. The process according to any one of embodiments 9 to 13, wherein: (a) the sesquiterpene is a guaiene, and which is for producing a guaiene-2-ol; or (b) the sesquiterpene is a guaiene-15-oic acid, optionally which is for producing a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. 15. The process according to any one of embodiments 5 to 14, wherein said mutant CYP102A enzyme further comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acids 171, 307, 319, 47 and / or 51 of SEQ ID NO: 2. 16. The process according to any one of embodiments 5 to 15, wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from H171L, Q307H, N319Y, R47L and / or Y51F of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme as one or more positions corresponding to the amino acid residues 171, 307, 319, 47 and / or 51 of SEQ ID NO: 2. 17. The process according to any one of embodiments 1 to 16, which comprises: contacting said sesquiterpene with a first mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a first sesquiterpene oxidation product; and contacting said sesquiterpene with a second mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a second sesquiterpene oxidation product; wherein said CYP102A enzymes comprises a heme monooxygenase domain comprising a P450 fold, and said first and second mutant CYP102A enzymes each comprise substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing oxygenase activity and / or altering product selectivity of the mutant enzyme. 18. The process according to embodiment 17, wherein the first mutant CYP102A enzyme is as defined in any one of embodiments 5 to 8, and the second mutant CYP102A enzyme is as defined in any one of embodiments 9 to 14. 19. The process according to any one of embodiments 9 to 14, 17 and 18, which further comprises acidifying and / or heating the oxidised sesquiterpene. 20. The process according to any one of embodiments 1 to 19, wherein the mutant CYP102A enzyme comprises a fusion of a heme monooxygenase domain to a reductase domain. 21. The process according to any one of embodiments 1 to 20, wherein the mutant CYP102A enzyme is a mutant CYP102A1 enzyme. 22. The process according to any one of embodiments 1 to 21, wherein a substrate:enzyme ratio of 1000:1 or less is used. 23. The process according to any one of embodiments 1 to 21, wherein a substrate:enzyme ratio of 1000:1 or more is used. 24. The process according to any one of embodiments 1 to 23, further comprising formulating the oxidised sesquiterpene in a fragrance, an aroma, an incense, a flavouring and / or a pharmaceutical composition. 25. A mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid. 26. The mutant CYP102A enzyme of embodiment 25, which is as defined in any one of embodiments 6, 7, 15 and 16. 27. A mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 181, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide. 28. The mutant CYP102A enzyme of embodiment 27, which is as defined in any one of embodiments 9 to 13, 15 and 16. 29. A kit or composition comprising: (a) the mutant CYP102A enzyme of embodiment 25 or 26; and (b) the mutant CYP102A enzyme of embodiment 27 or 28. 30. A composition comprising (a) the mutant CYP102A enzyme of embodiment 25 or 26, and / or the mutant CYP102A enzyme of embodiment 27 or 28; and (b) a sesquiterpene comprising fused 5- and 7-membered rings, such as a guaiene and / or a guaiene-15-oic acid. 31. One or more polynucleotides encoding an enzyme as defined in any one of embodiments 25 to 28, optionally in the form of a vector. 32. A cell which expresses an enzyme as defined in any one of embodiments 25 to 28. 33. Use of one or more enzymes as defined in any one of embodiments 25 to 28 for oxidizing a sesquiterpene comprising fused 5- and 7-membered rings. Informal Sequence Listing SEQ ID NO:1 (CYP102A1 nucleotide sequence) – acaattaaagaaatgcctcagccaaaaacgtttggagagcttaaaaatttaccgttattaaacacagataaaccggttcaagctttgatga aaattgcggatgaattaggagaaatctttaaattcgaggcgcctggtcgtgtaacgcgctacttatcaagtcagcgtctaattaaagaatg cgatgaatcacgctttgataaaaacttaagtcaagcggcacttaaatttgtacgtgattttgcaggagacgggttatttacaagctggacg catgaaaaaaattggaaaaaagcgcataatatcttacttccaagcttcagtcagcaggcaatgaaaggctatcatgcgatgatggtcgat atcgccgtgcagcttgttcaaaagtgggagcgtctaaatgcagatgagcatattgaagtaccggaagacatgacacgtttaacgcttga tacaattggtctttgcggctttaactatcgctttaacagcttttaccgagatcagcctcatccatttattacaagtatggtccgtgcactggat gaagcaatgaacaagctgcagcgagcaaatccagacgacccagcttatgatgaaaacaagcgccagtttcaagaagatatcaaggt gatgaacgacctagtagataaaattattgcagatcgcaaagcaagcggtgaacaaagcgatgatttattaacgcatatgctaaacggaa aagatccagaaacgggtgagccgcttgatgacgagaacattcgctatcaaattattacattcttaattgcgggacacgaaacaacaagt ggtcttttatcatttgcgctgtatttcttagtgaaaaatccacatgtattacaaaaagcagcagaagaagcagcacgagttctagtagatcc tgctccaagctacaaacaagtcaaacagcttaaatatgtcggcatggtcttaaacgaagcgctgcgcttatggccaactgctcctgcgtt ttccctatatgcaaaagaagatacggtgcttggaggagaatatcctttagaaaaaggcgacgaactaatggttctgattcctcagcttcac cgtgataaaacaatttggggagacgatgtggaagagttccgtccagagcgttttgaaaatccaagtgcgattccgcagcatgcgtttaa accgtttggaaacggtcagcgtgcgtgtatcggtcagcagttcgctcttcatgaagcaacgctggtacttggtatgatgctaaaacacttt gactttgaagatcatacaaactacgagctggatattaaagaaactttaacgttaaaacctgaaggctttgtggtaaaagcaaaatcgaaa aaaattccgcttggcggtattccttcacctagcactgaacagtctgccaaaaaagcacgcaaaaaggcagaaaacgctcataatacgc cgctgcttgtgctatacggttcaaatatgggaacagctgaaggaacggcgcgtgatttagcagatattgcaatgagcaaaggatttgca ccgcaggtcgcaacgcttgattcacacgccggaaatcttccgcgcgaaggagctgtattaattgtaacggcgtcttataacggtcatcc gcctgataacgcaaagcaatttgtcgactggttagaccaagcgtctgctgatgaagtaaaaggcgttcgctactccgtatttggatgcgg cgataaaaactgggctactacgtatcaaaaagtgcctgcttttatcgatgaaacgcttgccgctaaaggggcagaaaacatcgctgacc gcggtgaagcagatgcaagcgacgactttgaaggcacatatgaagaatggcgtgaacatatgtggagtgacgtagcagcctacttta acctcgacattgaaaacagtgaagataataaatctactctttcacttcaatttgtcgacagcgccgcggatatgccgcttgcgaaaatgca cggtgcgttttcaacgaacgtcgtagcaagcaaagaacttcaacagccaggcagtgcacgaagcacgcgacatcttgaaattgaactt ccaaaagaagcttcttatcaagaaggagatcatttaggtgttattcctcgcaactatgaaggaatagtaaaccgtgtaacagcaaggttc ggcctagatgcatcacagcaaatccgtctggaagcagaagaagaaaaattagctcatttgccactcgctaaaacagtatccgtagaag agcttctgcaatacgtggagcttcaagatcctgttacgcgcacgcagcttcgcgcaatggctgctaaaacggtctgcccgccgcataa agtagagcttgaagccttgcttgaaaagcaagcctacaaagaacaagtgctggcaaaacgtttaacaatgcttgaactgcttgaaaaat acccggcgtgtgaaatgaaattcagcgaatttatcgcccttctgccaagcatacgcccgcgctattactcgatttcttcatcacctcgtgtc gatgaaaaacaagcaagcatcacggtcagcgttgtctcaggagaagcgtggagcggatatggagaatataaaggaattgcgtcgaa ctatcttgccgagctgcaagaaggagatacgattacgtgctttatttccacaccgcagtcagaatttacgctgccaaaagaccctgaaac gccgcttatcatggtcggaccgggaacaggcgtcgcgccgtttagaggctttgtgcaggcgcgcaaacagctaaaagaacaaggac agtcacttggagaagcacatttatacttcggctgccgttcacctcatgaagactatctgtatcaagaagagcttgaaaacgcccaaagcg aaggcatcattacgcttcataccgctttttctcgcatgccaaatcagccgaaaacatacgttcagcacgtaatggaacaagacggcaag aaattgattgaacttcttgatcaaggagcgcacttctatatttgcggagacggaagccaaatggcacctgccgttgaagcaacgcttatg aaaagctatgctgacgttcaccaagtgagtgaagcagacgctcgcttatggctgcagcagctagaagaaaaaggccgatacgcaaaa gacgtgtgggctggg SEQ ID NO: 2 (CYP102A1 amino acid sequence) – TIKEMPQPKTFGELKNLPLLNTDKPVQALMKIADELGEIFKFEAPGRVTRYLSSQRLI KEACDESRFDKNLSQALKFVRDFAGDGLFTSWTHEKNWKKAHNILLPSFSQQAMKG YHAMMVDIAVQLVQKWERLNADEHIEVPEDMTRLTLDTIGLCGFNYRFNSFYRDQP HPFITSMVRALDEAMNKLQRANPDDPAYDENKRQFQEDIKVMNDLVDKIIADRKAS GEQSDDLLTHMLNGKDPETGEPLDDENIRYQIITFLIAGHETTSGLLSFALYFLVKNPH VLQKAAEEAARVLVDPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTV LGGEYPLEKGDELMVLIPQLHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQ RACIGQQFALHEATLVLGMMLKHFDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIP LGGIPSPSTEQSAKKVRKKAENAHNTPLLVLYGSNMGTAEGTARDLADIAMSKGFA PQVATLDSHAGNLPREGAVLIVTASYNGHPPDNAKQFVDWLDQASADEVKGVRYS VFGCGDKNWATTYQKVPAFIDETLAAKGAENIADRGEADASDDFEGTYEEWREHM WSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMHGAFSTNVVASKELQQPG SARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFGLDASQQIRLEAEEEK LAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVELEALLEKQAYK EQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDEKQASITVSVV SGEAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLIMVGPGTGV APFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIITLHTAFS RMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYADV HQVSEADARLWLQQLEEKGRYAKDVWAG SEQ ID NO: 3 (CYP102A1, residues 1-470): TIKEMPQPKTFGELKNLPLLNTDKPVQALMKIADELGEIFKFEAPGRVTRYLSSQRLI KEACDESRFDKNLSQALKFVRDFAGDGLFTSWTHEKNWKKAHNILLPSFSQQAMKG YHAMMVDIAVQLVQKWERLNADEHIEVPEDMTRLTLDTIGLCGFNYRFNSFYRDQP HPFITSMVRALDEAMNKLQRANPDDPAYDENKRQFQEDIKVMNDLVDKIIADRKAS GEQSDDLLTHMLNGKDPETGEPLDDENIRYQIITFLIAGHETTSGLLSFALYFLVKNPH VLQKAAEEAARVLVDPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTV LGGEYPLEKGDELMVLIPQLHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQ RACIGQQFALHEATLVLGMMLKHFDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIP LGGIPSPSTEQSAKKV SEQ ID NO: 4 (CYP102A2, P450 domain corresponding to 1-470 of CYP102A1): KETSPIPQPKTFGPLGNLPLIDKDKPTLSLIKLAEEQGPIFQIHTPAGTTIVVSGHELVKE VCDEERFDKSIEGALEKVRAFSGDGLFTSWTHEPNWRKAHNILMPTFSQRAMKDYH EKMVDIAVQLIQKWARLNPNEAVDVPGDMTRLTLDTIGLCGFNYRFNSYYRETPHP FINSMVRALDEAMHQMQRLDVQDKLMVRTKRQFRYDIQTMFSLVDSIIAERRANGD QDEKDLLARMLNVEDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFATYFLLKHPDK LKKAYEEVDRVLTDAAPTYKQVLELTYIRMILNESLRLWPTAPAFSLYPKEDTVIGG KFPITTNDRISVLIPQLHRDRDAWGKDAEEFRPERFEHQDQVPHHAYKPFGNGQRAC IGMQFALHEATLVLGMILKYFTLIDHENYELDIKQTLTLKPGDFHISVQSRHQEAIHA DVQAAEKAAP SEQ ID NO: 5 (CYP102A3, P450 domain corresponding to 1-470 of CYP102A1): KQASAIPQPKTYGPLKNLPHLEKEQLSQSLWRIADELGPIFRFDFPGVSSVFVSGHNL VAEVCDEKRFDKNLGKGLQKVREFGGDGLFTSWTHEPNWQKAHRILLPSFSQKAM KGYHSMMLDIATQLIQKWSRLNPNEEIDVADDMTRLTLDTIGLCGFNYRFNSFYRDS QHPFITSMLRALKEAMNQSKRLGLQDKMMVKTKLQFQKDIEVMNSLVDRMIAERK ANPDENIKDLLSLMLYAKDPVTGETLDDENIRYQIITFLIAGHETTSGLLSFAIYCLLT HPEKLKKAQEEADRVLTDDTPEYKQIQQLKYIRMVLNETLRLYPTAPAFSLYAKEDT VLGGEYPISKGQPVTVLIPKLHRDQNAWGPDAEDFRPERFEDPSSIPHHAYKPFGNGQ RACIGMQFALQEATMVLGLVLKHFELINHTGYELKIKEALTIKPDDFKITVKPRKTAA INVQRKEQADIKA SEQ ID NO: 6 (CYP102A4, P450 domain corresponding to 1-470 of CYP102A1): DKKVSAIPQPKTYGPLGNLPLIDKDKPTLSFIKLAEEYGPIFRMQTLSDTIIVVSGHELV AEVCDETRFDKSIEGALAKVRAFAGDGLFTSETQEPNWQKAHNILMPTFSQRAMKD YHAMMVDIAVQLVQKWARLNPNENVDVPEDMTRLTLDTIGLCGFNYRFNSFYRET PHPFITSMTRALDEAMHQLQRLDIEDKLMWRTKRQFQHDIQSMFSLVDNIIAERKSSE NQEENDLLSRMLNVQDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFAIYFLLKNPD KLKKAYEEVDRVLTDSTPTYQQVMKLKYIRMILNESLRLWPTAPAFSLYAKEDTVIG GKYPIKKGEDRISVLIPQLHRDKDAWGDNVEEFQPERFEELDKVPHHAYKPFGNGQR ACIGMQFALHEATLVMGMLLQHFEFIDYEEYQLDVKQTLTLKPGDFKIRIVPRNQTIS HTTVLAPTEE SEQ ID NO: 7 (CYP102A5, P450 domain corresponding to 1-470 of CYP102A1): EKKVSAIPQPKTYGPLGNLPLIDKDKPTLSFIKIAEEYGPIFQIQTLSDTIIVVSGHELVA EVCDETRFDKSIEGALAKVRAFAGDGLFTSETHEPNWKKAHNILMPTFSQRAMKDY HAMMVDIAVQLVQKWARLNPNENVDVPEDMTRLTLDTIGLCGFNYRFNSFYRETP HPFITSMTRALDEAMHQLQRLDIEDKLMWRTKRQFQHDIQSMFSLVDNIIAERKSSG DQEENDLLSRMLNVPDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFAIYFLLKNPD KLKKAYEEVDRVLTDPTPTYQQVMKLKYMRMILNESLRLWPTAPAFSLYAKEDTVI GGKYPIKKGEDRISVLIPQLHRDKDAWGDNVEEFQPERFEELDKVPHHAYKPFGNGQ RACIGMQFALHEATLVMGMLLQHFELIDYQNYQLDVKQTLTLKPGDFKIRILPRKQT ISHPTVLAPTED SEQ ID NO: 8 (CYP102A6, P450 domain corresponding to 1-470 of CYP102A1): SSKNRLDPIPQPPTKPVVGNMLSLDSAAPVQHLTRLAKELGPIFWLDMMGSPIVVVS GHDLVDELSDEKRFDKTVRGALRRVRAVGGDGLFTADTREPNWSKAHNILLQPFGN RAMQSYHPSMVDIAEQLVQKWERLNADDEIDVVHDMTALTLDTIGLCGFDYRFNSF YRRDYHPFVESLVRSLETIMMTRGLPFEQIWMQKRRKTLAEDVAFMNKMVDEIIAE RRKSAEGIDDKKDMLAAMMTGVDRSTGEQLDDVNIRYQINTFLIAGHETTSGLLSYT LYALLKHPDILKKAYDEVDRVFGPDVNAKPTYQQVTQLTYITQILKEALRLWPPAPA YGISPLADETIGGGKYKLRKGTFITILVTALHRDPSVWGPNPDAFDPENFSREAEAKR PINAWKPFGNGQRACIGRGFAMHEAALALGMILQRFKLIDHQRYQMHLKETLTMKP EGFKIKVRPRADRERGA SEQ ID NO: 9 (CYP102A7, P450 domain corresponding to 1-470 of CYP102A1): NKLDGIPIPKTYGPLGNLPLLDKNRVSQSLWKIADEMGPIFQFKFADAIGVFVSSHEL VKEVSEESRFDKNMGKGLLKVREFSGDGLFTSWTEEPNWRKAHNILLPSFSQKAMK GYHPMMQDIAVQLIQKWSRLNQDESIDVPDDMTRLTLDTIGLCGFNYRFNSFYREG QHPFIESMVRGLSEAMRQTKRFPLQDKLMIQTKRRFNSDVESMFSLVDRIIADRKQA ESESGNDLLSLMLHAKDPETGEKLDDENIRYQIITFLIAGHETTSGLLSFAIYLLLKHP DKLKKAYEEADRVLTDPVPSYKQVQQLKYIRMILNESIRLWPTAPAFSLYAKEETVI GGKYLIPKGQSVTVLIPKLHRDQSVWGEDAEAFRPERFEQMDSIPAHAYKPFGNGQR ACIGMQFALHEATLVLGMILQYFDLEDHANYQLKIKESLTLKPDGFTIRVRPRKKEA MTAMPGAQPEENG SEQ ID NO: 10 (CYP102A8, P450 domain corresponding to 1-470 of CYP102A1): DKKVSAIPQPKTYGPLGNLPLIDKDKPTLSFIKLAEEYGPIFQIQTLSDTIIVVSGHELV AEVCDETRFDKSIEGALAKVRAFAGDGLFTSETDEPNWKKAHNILMPTFSQRAMKD YHAMMVDIAVQLVQKWARLNPNENVDVPEDMTRLTLDTIGLCGFNYRFNSFYRET PHPFITSMTRALDEAMHQLQRLDIEDKLMWRTKRQFQHDIQSMFSLVDNIIAERKSSE NQEENDLLSRMLNVQDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFAIYFLLKNPD KLKKAYEEVDRVLTDSTPTYQQVMKLKYIRMILNESLRLWPTAPAFSLYAKEDTVIG GKYPIKKGEDRISVLIPQLHRDKDAWGDDVEEFQPERFEELDKVPHHAYKPFGNGQR ACIGMQFALHEATLVMGMLLQHFEFIDYEDYQLDVKQTLTLKPGDFKIRIVPRNQTIS HTTVLAPTEE SEQ ID NO: 11 (CYP102A9, P450 domain corresponding to 1-470 of CYP102A1): DKKVSAIPQPKTYGLLGNLPLIDKDKPTLSFIKIAEEYGPIFRIQTLSDTIIVVSGHELVA EVCDETRFDKSIEGALAKVRAFAGDGLFTSETHEPNWKKAHNILMPTFSQRAMKDY HAMMVDIAVQLVQKWARLNPNENVDVPEDMTRLTLDTIGLCGFNYRFNSYYRETP HPFITSMSRALDEAMHQLQRLDIEDKLMWRTKRQFQHDIQSMFSLVDNIIAERKSSG NQEENDLLSRMLNVQDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFAIYFLLKNPD KLKKAYEEVDRVLTDPTPTYQQVMKLKYIRMILNESLRLWPTAPAFSLYAKEDTVIG GKYPIKKGEDRISVLIPQLHRDKDAWGDNVEEFQPERFEELDKIPHHAYKPFGNGQR ACIGMQFALHEATLVMGMLLQHFEFIDYQDYQLDVKQTLTLKPGDFKIRILPRNQTIS HTTVLAPIEE SEQ ID NO: 12 (CYP102A10, P450 domain corresponding to 1-470 of CYP102A1): DAPTALAPIPQPPGKPIVGNAFTVDSSRLIQSLMELAEEYGPIFQLEVMGTPLVFVSGA DMVAEICDESRFDKTVRGPLKRLRLIAGDGLFTGDTDDPNWAKAHHILLPSFSQKAM GSYLPMMTDIASQLMLKWERLNSDDVIDVPMDMVRLTLDTIGVCGFGYRFNSFYRE DFHPFIEALNRTLDTTQKMRGLPGEKLLKRQQIEQLNEDAAYMNNLVDEIIRERRQT GESGQGDLLDFMLSGRDPVTGERLSDENIRYQINTFLIAGHETTSGLLSFTLYYLLKN RDVLQRAYAEVDEVLGRNIDQTPTLSQIGRLPYIRAILSEALRLWPTAPAMGLAPFED EVLGGKYAIAKGTFTTVLIPSLHRDKLVWGENPEAFNPDNFSPKAEAARPPHAYKPF GNGQRACIGRQFAIQESILVLGMLLQRFELFDHADYQLRIKETLSIKPDGFTIKARLRH DVERGGVAT SEQ ID NO: 13 (CYP102A11, P450 domain corresponding to 1-470 of CYP102A1): ATNATLTPIPQPPGKPLIGNALTVDASQQIQSLMELAEEYGPIFQLDMMGTPIVIISGA DLVAEVCDEKRFDKSVRGPLKRLRLIGGDGLFTGDTDAPNWSKAHNILLPSFSQKA MGSYLPMMTDIATQLVMKWERMNSDDVIDVPKDMIRLTLDTIGVCGFGYRFNSFYR EDFHPFIRALTRTLETTQKIRGIPGEKLLKGDAVKQLHRDAKYMNNLVDEIIRERQRS GGDGPEDLLDFMLSGRDPLTGERLSDENIRYQINTFLIAGHETTSGLLSFTLYYLLKN RDVLTRAYAEVDTVLGRNIDQPPSLKQIGQLPYIRAILFEALRLWPTAPAFGLAPFED EVLGGKYLIPKGTFTTVLIPSLHRDKSVWGENPEVFDPENFTAEAEAARPPHAYKPFG NGQRACIGRQFAIQESILVLAMILQRFELFDHSDYKLDIKETLSIKPDEFTIKARMRKD VERGGKAT SEQ ID NO: 14 (CYP102A12, P450 domain corresponding to 1-470 of CYP102A1): SSSNKLAPIPHPPKQPVVGNMLSIDTKAPVQHLVRLAEELGPIFWLDMMGAPIVIVSG YDLVDEISDEKRFDKAVRGALRRVRTVGGDGLFTADTSEPNWSKAHNILLTPFGGR AMQSYHPSMVDIAEQLVKKWERLNADDEIDVVHDMTALTLDTIGLCGFDYRFNSFY RRDYHPFVESLVRSLETIMMTRGLPLENLWMKKRRDTLAEDVAFMNAMVDEIIAER RKAAAVADKMDMLGAMMTGVDKVTGEPLDDVNIRYQINTFLIAGHETTSGLLSCAI YALLKHPEVLQKAYDEVDRVLGADTSVEPSYQQVNQLGYITQILKETLRLWPPAPA YGVAPIQDETIGGQYHLKRGTFTTVLVLALHRDPSIWGPNPDAFDPENFSREAESKRP ANAWKPFGNGQRACIGRGFAMHEAALALGMILQRFKLIDHTRYRMVLKETLTIKPE GFKIKVRPRSDKDRATRI SEQ ID NO: 15 (CYP102A13, P450 domain corresponding to 1-470 of CYP102A1): ASNNKMSPIPQPPTRPVVGNMLSLDSAAPVQDLTRLAKELGPIFWLDMMGAPIVIVS GYTLVDELSVETRLDKVVRGALRRVRAIGGDGLFTADTAEPNWSKARNILLQPFGN RAMQSYHPSMVDIAEQLVKKWERLNADDEIDVVHDMTALTLDTIGLCGFDYRFNSF YRRDYHPFVESLVRSLETIMMIRGLPLENFWMRRRRSDLATDVAFMNKMVDEIVAE RRKSAEASDGKKDMLNAMMSGVDRSTGEQLDDVNIRYQINTFLIAGHETTSGLLSY AIYALLKHPDVLKKAYAEVDRVLGADIEARPSYQQVTQLTYITQILKEALRLWPPAP AYGIAPLKDETIAGGKYSLKKNTFISILVTALHHDPAVWGPNPDLFDPENFSPEAEAK RPVNAWRPFGNGQRACIGRGFAMHEAALALGMILQRFKLIDHQRYQIRLKETLTIKP DGFKIKVRPRSGHDRTV SEQ ID NO: 16 (CYP102A14, P450 domain corresponding to 1-470 of CYP102A1): ASNNKMSPIPQPPTRPVVGNMLSLDSAAPVQDLTRLAKELGPIFWLDMMGAPIVIVS GYTLVDELSVETRLDKVVRGALRRVRAIGGDGLFTADTAEPNWSKARNILLQPFGN RAMQSYHPSMVDIAEQLVKKWERLNADDEIDVVHDMTALTLDTIGLCGFDYRFNSF YRRDYHPFVESLVRSLETIMMIRGLPLENFWMRRRRSDLATDVAFMNKMVDEIVAE RRKSAEASDGKKDMLNAMMSGVDRSTGEQLDDVNIRYQINTFLIAGHETTSGLLSY AIYALLKHPDVLKKAYAEVDRVLGADIEARPSYQQVTQLTYITQILKEALRLWPPAP AYGIAPLKDETIAGGKYSLKKNTFISILVTALHHDPAVWGPNPDLFDPENFSPEAEAK RPVNAWRPFGNGQRACIGRGFAMHEAALALGMILQRFKLIDHQRYQIRLKETLTIKP DGFKIKVRPRSGHDRTV SEQ ID NO: 17 (CYP102A15, P450 domain corresponding to 1-470 of CYP102A1): QQTSIIPKPKTYGPFKNIPHIKKGELSQTFWRLADELGPIFQFEFSKATSIFVSNHELFQ EICDESRFDKYIGTSLNKVRAFAGDGLFTSWTEEPNWRKAHHILMPAFSQQAMKGY HEMMLDIATQLVQKWQRTGRDEEIEVAEDMTKLTLDTIGLCGFDFRFNSFYKENQH PFIESMVNGLSEAMDQASRLPVADKLMIKRRKKFEENVDFMKQLVDDIIQERKKQD KTGDDLLSLMLHAKDPETGERLSDENIRYQIITFLIAGHETTSGLLSFAIYFLLKNPEK LKKAVQEADDVLQGGLPTFKQVQKLNYTRMVLNESLRLWPTAPTFSLYAKEDTVIG GKYSIEKNQSVSVLLPKLHRDQAVWGEDAEEFKPERFLHPEKIPQHAYKPFGNGQRA CIGMQFALHEATMVLAMVLHNLELIDHTSYELDLKESLTIKPNDFKIKVRPRKQQLF MVPPKEETKKSTT SEQ ID NO: 18 (CYP102A16, P450 domain corresponding to 1-470 of CYP102A1): DKKVSAIPQPKTYGPLGNLPLIDKDKPTLSFIKLAEEYGPIFQIQTLSDTIIVVSGHELV AEVCDETRFDKSIEGALAKVRAFAGDGLFTSETHEPNWKKAHNILMPTFSQRAMKD YHAMMVDIAVQLVQKWARLNPNENVDVPGDMTRLTLDTIGLCGFNYRFNSFYRET SHPFITSMTRALDEAMHQLQRLDIEDKLMWRTKRQFQHDIQSMFSLVDNIIAERKSS GNQEENDLLSRMLHVQDPETGEKLDDENIRFQIITFLIAGHETTSGLLSFAIYFLLKNP DKLKKAYEEVDRVLTDPTPTYQQVMKLKYIRMILNESLRLWPTAPAFSLYAKEDTVI GGKYPIKKGEDRISVLIPQLHRDKDAWGDNVEEFQPERFEELDKVPHHAYKPFGNGQ RACIGMQFALHEATLVMGMLLQHFEFIDYEDYKLDVKQTLTLKPGDFKIRIVPRNQT ISHTTVLAPTEE SEQ ID NO: 19 (CYP102A25, P450 domain corresponding to 1-470 of CYP102A1): AAKQESKKHDDKHKGQIPGPKGLPIIGSLLDIDLTDSLKSIIDMAKDYPKLFALNIGGN TEVMICSRELMDELSDESRFHKLVVGGVEKLRPLAGDGLFSAQHNNQEWAIAHRIL MPLFGPLTIREMFPDMRDISEQLCLKWARLGSSSTIDVGNDFTRLTLDTIALCTMGFR FNSFYSNDKMHPFVESMVAALIDAEKQSFLPDVVQSLRIRAQSHFKKHAAVMKSTC QDILDQRRKNPVEGKDLLNAMMNGKDPKTGMGMSDGNIVDNLITFLIAGHETTSGL LSFAFYYLLENPEKLQRAREEVDEVLGDENITADHLPKMPYINMIFRETLRLMPTAPG FYVTPFKDEVIGGQYNVSAGDPLFLFLHMIHRDPEVWGPDAEEFRPERMADEHFNKL PKNAWKPFGNGMRGCIGREFAWQEAQIVTIMLLQNFDMVKADPNYKLKIKQSLTIK PDGFNMKVKLREGR SEQ ID NO: 20 (CYP102A26, P450 domain corresponding to 1-470 of CYP102A1): TQTHRTIPQAKSYGPLGSLPLIDREKPIQSFLKLADVYGPIYQFQYPGKQSTFVSGYNL VKELSDESRFDKKVGPALQKVRAFGGDGLFTSETNEANWKKAHNILLPSFSQQAMK GYHDKMTDLAVQLVQKWARLNPNETADVPEDMTRLTLDTIGLCGFNYRFNSFYRE TNHWFVDSMVRALDESMNQLQRLGIQDKLMVKAKRQFDQDIHDMFSLVDQLIAER KAAGDQGEDDLLAHMLKGKDPETGEQLSDENIRFQIITFLIAGHETTSGMLSFAIYYL MKNPDKLQKAYEEVDEVFGDQGVPSYKQVKQLKYVRNVLNESLRLWPTAPAFALY AKDDTTLGDDYHLEKGQTAVILTPALHRDQSVWGDDVESFKPERFENPQDIPQHAF KPFGNGQRACIGQQFAMHEATLVLGMLLQNFEFIDHADYELEIKESLTLKPDGMTIQ VKQRKPLNLTRATDEHNAE SEQ ID NO: 21 (Krac9955 (A.K.A. CYP102A18), P450 domain corresponding to 1- 470 of CYP102A1): LRSQLDTIPMGDMKEVHPESAVRDLIKQAQRHGPIFQLPLPDGTRRIVLSSFALVDEV CNDQFFDKRVSVNVRNLRSAIGSGLFSADTSDPNWRKAHTILMPSFSLQAMRNYEP MMVDAAEQLMAKWEHLNPEDLINVPDDMTRVTLETIGLCGFSYHFHAITREQMHPF VEAMVHILSTTAARATRPPIEEKLRFRQRRQLQADLDLLLSTADQLVRERKMMGTE GQKYNDLLNAMLNGIDKQTGEKLDDVNIRNQIITFLIAGHETTSGLLSFATYFLLHHP DVLNRAYEEVDRVLGRDTRKTPTYEQIHQLVYIKQILKETLRLCPTAPMFNRYPYEE RPLAGKYQLQPSDTITVLTPMLHRDRSIWGDDAEIFNPDHHFNPEAEKQRPANAYKP FGTGQRSCIGREFALQEATLVLGMMLQRFYPYTTGIYQLKIREALTIKPADFYMRVRP RTDIDHIIITPLDE SEQ ID NO: 22 (Krac0936 (A.K.A. CYP102A18), P450 domain corresponding to 1- 470 of CYP102A1): QIEEKTLVSIPQPQKKPLVGNLYSLDHALPTLSMMDLARELGPIYQLEIPGRRTVIVSG FELADELSDETRFDKRVWRPLQNVRAFAGDGLFTAYTQEANWHKAHNILLPNFSMR AMQGYIPMMQDIAEQLLGKWERMNANEEIDVVSDMTRLTLDTIGLCGFDYRFNSFY REDLHPFIQSMGNALGESMARGRRLALQEKLMVNKHRQFQADVDFMNNLVDQVIR ERKAGGENAQKKDLLSYMLSGVDKQSGEGLNDVNIRYQIITFLIAGHETTSGLLSFSL YFLLKHPEVLAKAYDEVDRVLGPDTSAKPTFQQINKLQYVSQILKESLRLWPTAPLFS VYPYEETVVGDKYRMDKDSEWAILIPMLHRDKSVWGEDADEFNPDHFSHEAEASRP ANAYKPFGNGERACIGRQFAMQEATLVLGQILQRFNLLDPHNYELKIKQTLTLKPEG FTMKVRKRSDAERNL SEQ ID NO: 23 (CYP102B1, P450 domain corresponding to 1-470 of CYP102A1): AQTAREPARDGLPKGFRSAELGWPELHRIPHPPYRLPLLGDVVGASRRTPMQDSLRY ARRLGPIFRRRAFGKEFVFVWGAALAADLADEARFAKHVGLGVANLRPVAGDGLFT AYNHEPNWQLAHDVLAPGFSREAMAGYHVMMLDVAARLTGHWDLAEASGRAVD VPGDMTKLTLETIARTGFGHDFGSFERSRLHPFVTAMVGTLGYAQRLNTVPAPLAP WLLRDASRRNAADIAHLNRTVDDLVRERRANGGTGGGTGSGSGSGDLLDRMLETA HPRTGERLSPQNVRRQVITFLVAGHETTSGALSFALHYLAQHPDVAARARAEVDRV WGDTEAPGYEQVAKLRYVRRVLDESLRLWPTAPGFAREAREDTVLGGTHPMRRGA WALVLTGMLHRDPEVWGADAERFDPDRFDAKAVRSRAPHTFKPFGTGARACIGRQ FALHEATLVLGLLLRRYELRPEPGYRL

Claims

CLAIMS 1. A process for oxidising a sesquiterpene comprising fused 5- and 7-membered rings, comprising contacting said sesquiterpene with a mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing oxygenase activity and / or altering product selectivity of the mutant enzyme.

2. The process according to claim 1, wherein the sesquiterpene is a guaiene, a cedrene or a patchoulene.

3. The process according to claim 2, wherein the guaiene is δ-guaiene.

4. The process according to claim 2 or 3, which is for producing a guaiene-15-ol, a guaiene-15-al, a guaiene-15-oic acid, a guaiene-2-ol, a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide.

5. The process according to any one of claims 1 to 4, wherein said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, optionally wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from A82I, A82M, F87I, A184I, A184M, A184F, T260L, T260G, V26L, V26M, L71M, S72V, S72I, S72L, S72A, S72W, A74L, V78I, T88L, T88F, T88M, L181F, I263A, I263G, E267V, A328I, A330V, A330I, A330F, A330P and / or A330W of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme as one or more positions corresponding to the amino acid residues 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO:

2.

6. The process according to any one of claims 1 to 5, wherein said mutant CYP102A enzyme comprises one of the following groups of substitutions in SEQ ID NO: 2:i. F87I; ii. A82M; iii. A82M / T260G; iv. A184I / T260G; v. A82M / A184I / T260G; vi. F87I / V26L; vii. F87I / V26M; viii. F87I / L71M; ix. F87I / S72V; x. F87I / S72I xi. F87I / S72L; xii. F87I / A74L; xiii. F87I / A82I; xiv. F87I / A82M; xv. F87I / T88L; xvi. F87I / T88F; xvii. F87I / T88M; xviii. F87I / L181F; xix. F87I / A184F; xx. F87I / A184I; xxi. F87I / A184M; xxii. F87I / T260G; xxiii. F87I / T260L; xxiv. F87I / A330V; xxv. F87I / A330I; xxvi. F87I / A330F; xxvii. F87I / A330W; xxviii. F87I / A330P; xxix. F87I / A184I / V26L; xxx. F87I / A184I / V26M; xxxi. F87I / A184I / S72L; xxxii F87I / A184I / A82M; xxxiii. F87I / A184I / A330I; xxxiv. F87I / A184I / A330V;xxxv. F87I / A82M / A330I; xxxvi. F87I / A82M / A330V; xxxvii. F87I / A82M / A184I; xxxviii. F87I / A82M / A330I / A184I; xxxix. F87I / A82M / A330V / A184I; xl. F87I / A82M / A330I / V26L; xli. F87I / A82M / A330V / V26L; xlii. F87I / A82M / A330I / V26M; xliii. F87A / A328I; xliv. F87A / A328I / S72A; xlv. F87A / A328I / S72W; xlvi F87A / A328I / V78I; xlvii. F87L / I263G; xlviii. A184I / A328L; xlix. E267V; l. E267V / I263A; li. E267V / V78I; lii. A330W; liii. A330W / S72G; or liv. A330W / S72W; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed in i. to liv.

7. The process according to claim 5 or 6, wherein the sesquiterpene is a guaiene, and which is for producing a guaiene-15-ol, a guaiene-15-al and / or a guaiene-15-oic acid.

8. The process according to any one of claims 1 to 4, wherein said mutant CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437, optionally wherein said mutant CYP102A enzyme comprises substitutions in the polypeptide chain of a wild-type CYP102A enzyme at a position corresponding to amino acid residue position 87 of SEQ ID NO:2, and at one or more positions corresponding to aminoacid residue positions 72, 78, 82, 178, 184, 263, 264, 267, 328, 330 and / or 437 of SEQ ID NO:

2.

9. The process according to any one of claims 1 to 4 and 8, wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from F87A, F87L, F87V, L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild- type CYP102A enzyme at one or more positions corresponding to the amino acid residues 87, 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2, optionally wherein said mutant CYP102A enzyme comprises a substitution selected from F87A, F87L, F87V, and one or more substitution(s) selected from L71F, L71M, S72G, S72W, V78A, V78I, A82M, V178F, A184I, I263A, I263G, A264G, E267F, A328F, A328G, A328I, A328L, A330I, A330P, A330W, S332M, L437F and / or L437M of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at position 87 and at one or more positions corresponding to the amino acid residues 71, 72, 78, 82, 178, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO:

2.

10. The process according to any one of claims 1 to 4 and 8 to 9, wherein said mutant CYP102A enzyme comprises one of the following groups of substitutions in SEQ ID NO: 2: i. F87A / A184I; ii. F87A / I263G; iii. F87A / A330P; iv. F87A / A184I / A330P v. F87A / A184I / I263G / A264G / A328G; vi. F87A / A184I / I263G / A330P; vii. F87A / A184I / I263G / A264G / A330P; viii. F87A / I263G / A264G; ix. F87A / I263G / A330P; x. F87A / A184I / I263G / A264G; xi. F87A / A184I / I263G / A328G; xii. F87A / A328I; xiii. F87A / A328L; xiv F87V / V78I;xv. F87V / A264G; xvi. F87I / A82M / A184I / A330I / L71F; xvii. F87I / A82M / A184I / A330I / L71M; xviii. F87I / A82M / A184I / A330I / V178F; xix. F87I / A82M / A184I / A330I / V78A / S332M; xx. F87I / A82M / A184I / A330I / L437F; xxi. F87I / A82M / A184I / A330I / L437M; xxii. F87L / I263G; xxiii. F87L / I263G / A328F; xxiv. I263G xxv. I263G / S72G; xxvi. I263G / S72W; xxvii. I263G / A82M; xxvii. I263G / A184I; xxix. I263G / A264G / A328G xxx. E267F xxxi. A330P; xxxii. A330W; xxxiii. A330W / S72G; xxxiv. A330W / A82M; or xxxv. A330W / A82M / I263A; or corresponding substitutions in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to the amino acid residue positions of SEQ ID NO: 2 as listed in i. to xxxv.

11. The process according to any one of claims 8 to 10, wherein: (a) the sesquiterpene is a guaiene, and which is for producing a guaiene-2-ol; or (b) the sesquiterpene is a guaiene-15-oic acid, optionally which is for producing a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide.

12. The process according to any one of claims 5 to 11, wherein said mutant CYP102A enzyme further comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acids 171, 307, 319, 47 and / or 51 of SEQ ID NO: 2,optionally wherein said mutant CYP102A enzyme comprises one or more substitution(s) selected from H171L, Q307H, N319Y, R47L and / or Y51F of SEQ ID NO: 2, or corresponding substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme as one or more positions corresponding to the amino acid residues 171, 307, 319, 47 and / or 51 of SEQ ID NO:

2.

13. The process according to any one of claims 1 to 12, which comprises: contacting said sesquiterpene with a first mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a first sesquiterpene oxidation product; and contacting said sesquiterpene with a second mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme to produce a second sesquiterpene oxidation product; wherein said CYP102A enzymes comprises a heme monooxygenase domain comprising a P450 fold, and said first and second mutant CYP102A enzymes each comprise substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions, thereby enhancing oxygenase activity and / or altering product selectivity of the mutant enzyme, optionally wherein the first mutant CYP102A enzyme is as defined in any one of claims 5 to 7, and the second mutant CYP102A enzyme is as defined in any one of 8 to 11.

14. The process according to any one of claims 8 to 11 and 13, which further comprises acidifying and / or heating the oxidised sesquiterpene.

15. The process according to any one of claims 1 to 14, wherein the mutant CYP102A enzyme: (a) comprises a fusion of a heme monooxygenase domain to a reductase domain; and / or (b) is a mutant CYP102A1 enzyme.

16. The process according to any one of claims 1 to 15, wherein a substrate:enzyme ratio of 1000:1 or less is used.

17. The process according to any one of claims 1 to 15, wherein a substrate:enzyme ratio of 1000:1 or more is used.

18. The process according to any one of claims 1 to 17, further comprising formulating the oxidised sesquiterpene in a fragrance, an aroma, an incense, a flavouring and / or a pharmaceutical composition.

19. A mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residues positions 82, 87, 184, 260, 26, 71, 72, 74, 78, 88, 181, 263, 267, 328, and / or 330 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-15-ol, a guaiene-15-al or a guaiene-15-oic acid, optionally wherein the mutant CYP102A enzyme is as defined in any one of claims 5, 6 and 12.

20. A mutant CYP102A (Cytochrome P450 family 102A sub-family member) enzyme, wherein said CYP102A enzyme comprises a heme monooxygenase domain comprising a P450 fold, and said mutation CYP102A enzyme comprises substitution(s) in the polypeptide chain of a wild-type CYP102A enzyme at one or more positions corresponding to amino acid residue positions 87, 71, 72, 78, 82, 181, 184, 263, 264, 267, 328, 330, 332 and / or 437 of SEQ ID NO: 2, wherein said mutant CYP102A enzyme is capable of oxidising a guaiene to a guaiene-2-ol and / or is capable of oxidising a guaiene-15-oic acid to a guaiene-2-ol-15-oic acid and / or a guaiene-15,2-olide, optionally wherein the mutant CYP102A enzyme is as defined in any one of claims 9, 10 and 12.

21. A kit or composition comprising: (a) the mutant CYP102A enzyme of claim 19; and (b) the mutant CYP102A enzyme of claim 20.

22. A composition comprising (a) the mutant CYP102A enzyme of claim 19, and / or the mutant CYP102A enzyme of claim 20; and (b) a sesquiterpene comprising fused 5- and 7- membered rings, such as a guaiene and / or a guaiene-15-oic acid.

23. One or more polynucleotides encoding an enzyme as defined in claim 19 or 20, optionally in the form of a vector.

24. A cell which expresses an enzyme as defined in claim 19 or 20.

25. Use of one or more enzymes as defined in claim 19 or 20 for oxidizing a sesquiterpene comprising fused 5- and 7-membered rings.

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