This review article focuses mainly on the scientific developments concerning the enzyme-mediated synthesis of sesquiterpenes which have been reported in the academic and patent literature during the last twenty years. Nevertheless, this is not a comprehensive description of every single biotransformation involving sesquiterpenes. Only synthetic approaches that have represented a new and innovative perspective from a scientific standpoint are reported. More specifically, the review describes in depth how the use of metabolic engineering of the microbial biotransformations and of the isolated enzymes were exploited in order to perform chemo- and stereoselective chemical transformations of interest for sesquiterpenes synthesis.
WithersS, KeaslingJ. (2007) Biosynthesis and engineering of isoprenoid small molecules. Applied Microbiology and Biotechnology, 73, 980–990
4.
KirbyJ, KeaslingJD. (2008) Metabolic engineering of microorganisms for isoprenoid production. Natural Product Reports, 25, 656–661
5.
MisawaN. (2011) Pathway engineering for functional isoprenoids. Current Opinion in Biotechnology, 22, 627–633
6.
LangeBM, AhkamiA. (2013) Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes-current status and future opportunities. Plant Biotechnology Journal, 11, 169–196.
7.
WangC, YoonS-H, JangH-J, ChungY-R, KimJ-Y, ChoiE-S, KimS-W. (2011) Metabolic engineering of Escherichia coli for α-farnesene production. Metabolic Engineering, 13, 648–655.
8.
Peralta-YahyaPP, OuelletM, ChanR, MukhopadhyayA, KeaslingJD, LeeTS. (2011) Identification and microbial production of a terpene-based advanced biofuel. Nature Communications, 2, 483.
9.
ChandranSS, KealeyJT, ReevesCD. (2011) Microbial production of isoprenoids. Process Biochemistry, 46, 1703–1710.
10.
SurburgH, PantenJ. (2006) Common fragrance and flavor materials: Preparation, Properties and Uses, WILEY-VCH, Weinheim
11.
SerraS, FugantiC, BrennaE. (2005) Biocatalytic preparation of natural flavours and fragrances. Trends in Biotechnology, 23, 193–198.
12.
GoldbergL, HaklaiR, BauerV, HeissA, KloogY. (2008) New derivatives of farnesylthiosalicylic acid (Salirasib) for cancer treatment: Farnesylthiosalicylamide inhibits tumor growth in nude mice models. Journal of Medicinal Chemistry, 52, 197–205.
13.
VladPF, UngurND, HungN, PerutskyVB. (1995) Superacidic low-temperature cyclization of terpenols and their acetates. Russian Chemical Bulletin, 44, 2390–2403.
14.
SchäferB. (2011) Ambrox®. Chemie in unserer Zeit, 45, 374–388.
15.
TanimotoH, OritaniT. (1996) Practical synthesis of Ambrox® from farnesyl acetate involving lipase catalyzed resolution. Tetrahedron: Asymmetry, 7, 1695–1704.
WiesnerJ, OrtmannR, JomaaH, SchlitzerM. (2003) New antimalarial drugs. Angewandte Chemie International Edition, 42, 5274–5293.
20.
FlanneryEL, ChatterjeeAK, WinzelerEA. (2013) Antimalarial drug discovery - approaches and progress towards new medicines. Nature Reviews Microbiology, 11, 849–862.
21.
ZengQ, QiuF, YuanL. (2008) Production of artemisinin by genetically-modified microbes. Biotechnology Letters, 30, 581–592.
22.
LiuB, WangH, DuZ, LiG, YeH. (2011) Metabolic engineering of artemisinin biosynthesis in Artemisia annua L. Plant Cell Reports, 30, 689–694.
CaneDE. (1990) Enzymic formation of sesquiterpenes. Chemical Reviews, 90, 1089–1103.
25.
ChristiansonDW. (2006) Structural biology and chemistry of the terpenoid cyclases. Chemical Reviews, 106, 3412–3442
26.
MillerDJ, AllemannRK. (2012) Sesquiterpene synthases: Passive catalysts or active players?Natural Product Reports, 29, 60–71.
27.
MelilloE, SetroikromoR, QuaxW, KayserO. (2013) Production of alpha-cuprenene in Xanthophyllomyces dendrorhous: a step closer to a potent terpene biofactory. Microbial Cell Factories, 12, 13.
28.
ReinsvoldRE, JinkersonRE, RadakovitsR, PosewitzMC, BasuC. (2011) The production of the sesquiterpene beta-caryophyllene in a transgenic strain of the cyanobacterium Synechocystis. Journal of Plant Physiology, 168, 848–852.
29.
HaradaH, YuF, OkamotoS, KuzuyamaT, UtsumiR, MisawaN. (2009) Efficient synthesis of functional isoprenoids from acetoacetate through metabolic pathway-engineered Escherichia coli. Applied Microbiology and Biotechnology, 81, 915–925.
30.
MartinVJJ, YoshikuniY, KeaslingJD. (2001) The in vivo synthesis of plant sesquiterpenes by Escherichia coli. Biotechnology and Bioengineering, 75, 497–503.
31.
NakanoC, TezukaT, HorinouchiS, OhnishiY. (2012) Identification of the SGR6065 gene product as a sesquiterpene cyclase involved in (+)-epicubenol biosynthesis in Streptomyces griseus. The Journal of Antibiotics, 65, 551–558.
32.
CaneDE, IkedaH. (2011) Exploration and mining of the bacterial terpenome. Accounts of Chemical Research, 45, 463–472.
33.
AttiaM, KimS-U, RoD-K. (2012) Molecular cloning and characterization of (+)-epi-α-bisabolol synthase, catalyzing the first step in the biosynthesis of the natural sweetener, hernandulcin, in Lippia dulcis. Archives of Biochemistry and Biophysics, 527, 37–44.
34.
PyleBW, TranHT, PickelB, HaslamTM, GaoZZ, MacNevinG, VederasJC, KimSU, RoDK. (2012) Enzymatic synthesis of valerena-4,7(11)-diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis). FEBS Journal, 279, 3136–3146.
35.
JacksonBE, Hart-WellsEA, MatsudaSPT. (2003) Metabolic engineering to produce sesquiterpenes in yeast. Organic Letters, 5, 1629–1632.
36.
ScalcinatiG, PartowS, SiewersV, SchalkM, DavietL, NielsenJ. (2012) Combined metabolic engineering of precursor and co-factor supply to increase alpha-santalene production by Saccharomyces cerevisiae. Microbial Cell Factories, 11, 117.
37.
SeitzM, SyrénP-O, SteinerL, KlebensbergerJ, NestlBM, HauerB. (2013) Synthesis of heterocyclic terpenoids by promiscuous squalene–hopene cyclases. ChemBioChem, 14, 436–439.
38.
HoshinoT, KumaiY, KudoI, NakanoS-i, OhashiS. (2004) Enzymatic cyclization reactions of geraniol, farnesol and geranylgeraniol, and those of truncated squalene analogs having C20 and C25 by recombinant squalene cyclase. Organic & Biomolecular Chemistry, 2, 2650–2657.
39.
YonemuraY, OhyamaT, HoshinoT. (2012) Chemo-enzymatic syntheses of drimane-type sesquiterpenes and the fundamental core of hongoquercin meroterpenoid by recombinant squalene-hopene cyclase. Organic & Biomolecular Chemistry, 10, 440–446.
40.
HollmannF, ArendsIWCE, HoltmannD. (2011) Enzymatic reductions for the chemist. Green Chemistry, 13, 2285–2314.
41.
MatsudaT, YamanakaR, NakamuraK. (2009) Recent progress in biocatalysis for asymmetric oxidation and reduction. Tetrahedron: Asymmetry, 20, 513–557.
42.
FronzaG, FugantiC, SerraS. (2009) Stereochemical course of Baker's yeast mediated reduction of the tri- and tetrasubstituted double bonds of substituted cinnamaldehydes. European Journal of Organic Chemistry, 6160–6171
43.
BrennaE, GattiFG, MontiD, ParmeggianiF, SerraS. (2012) Stereochemical outcome of the biocatalysed reduction of activated tetrasubstituted olefins by old yellow enzymes 1–3. Advanced Synthesis & Catalysis, 354, 105–112.
44.
DasB, VenkataiahB, KashinathamA. (1999) Chemical and biochemical modifications of parthenin. Tetrahedron, 55, 6585–6594.
45.
FugantiC, SerraS, DulioA. (1999) Baker's yeast mediated enantioselective synthesis of the bisabolane sesquiterpenes curcumene, turmerone, dehydrocurcumene and nuciferal. Journal of the Chemical Society, Perkin Transactions1, 279–282.
46.
FugantiC, SerraS. (2000) Baker's yeast-mediated enantioselective synthesis of the bisabolane sesquiterpenes (+)-curcuphenol, (+)-xanthorrhizol, (-)-curcuquinone and (+)-curcuhydroquinone. Journal of the Chemical Society, Perkin Transactions1, 3758–3764.
47.
SerraS. (2012) Enantioselective synthesis of the bisabolane sesquiterpene (+)-1-hydroxy-1,3,5-bisabolatrien-10-one and revision of its absolute configuration. Natural Product Communications, 7, 455–458.
48.
FugantiC, SerraS. (2000) Baker's yeast mediated enantioselective synthesis of the bisabolene sesquiterpenes (+)-epijuvabione and (-)-juvabione. Journal of the Chemical Society, Perkin Transactions1, 97–101.
49.
NakamuraK, YamanakaR, MatsudaT, HaradaT. (2003) Recent developments in asymmetric reduction of ketones with biocatalysts. Tetrahedron: Asymmetry, 14, 2659–2681.
50.
TaberDF, BaiS, TianW. (2011) Synthesis of the reported structure of trans-africanan-1α-ol. The Journal of Organic Chemistry, 76, 9733–9737.
MoriK, WatanabeH. (1986) Synthesis of both the enantiomers of polygodial, an insect antifeedant sesquiterpene. Tetrahedron, 42, 273–281.
53.
InoueT, HosomiK, ArakiM, NishideK, NodeM. (1995) Enantioselective reduction of σ-symmetric bicyclo[3.3.0]octane-2,8-diones with baker's yeast. Tetrahedron: Asymmetry, 6, 31–34.
54.
ZhuY-Y, Jean BurnellD. (1996) Enantio- and diastereoselectivity in the reduction of spiro[4.5]decane-1,4-dione derivatives with baker's yeast. Tetrahedron: Asymmetry, 7, 3295–3304.
55.
KatohT, MizumotoS, FudesakaM, TakeoM, KajimotoT, NodeM. (2006) An efficient route for the synthesis of methyl (-)-1,4a-dimethyl-5-oxodecahydronaphthalene-1-carboxylate by using baker's yeast-catalyzed asymmetric reduction. Tetrahedron: Asymmetry, 17, 1655–1662.
56.
FujiedaS, TomitaM, FuhshukuK, OhbaS, NishiyamaS, SugaiT. (2005) Chemoenzymatic route to both enantiomers of a 1-isopropyl-3a-methyloctahydroinden-4-one derivative: A synthetic intermediate for sesqui- and diterpenoids. Advanced Synthesis & Catalysis, 347, 1099–1109.
57.
HollmannF, ArendsIWCE, BuehlerK, SchallmeyA, BuhlerB. (2011) Enzyme-mediated oxidations for the chemist. Green Chemistry, 13, 226–265.
58.
PazminoDET, DudekHM, FraaijeMW. (2010) Baeyer-Villiger monooxygenases: recent advances and future challenges. Current Opinion in Chemical Biology, 14, 138–144.
59.
HudlickyT, GonzalezD, GibsonDT. (1999) Enzymatic dihydroxylation of aromatics in enantioselective synthesis: Expanding asymmetric methodology. Aldrichimica Acta, 32, 35–62.
60.
BorgesKB, BorgesWS, Durán-PatrónR, PupoMT, BonatoPS, ColladoIG. (2009) Stereoselective biotransformations using fungi as biocatalysts. Tetrahedron: Asymmetry, 20, 385–397.
61.
BanwellMG, HocklessDCR, McLeodMD. (2003) Chemoenzymatic total syntheses of the sesquiterpene (-)-patchoulenone. New Journal of Chemistry, 27, 50–59.
62.
BonDJYD, BanwellMG, WillisAC. (2010) A chemoenzymatic total synthesis of the hirsutene-type sesquiterpene (+)-connatusin B from toluene. Tetrahedron, 66, 7807–7814.
63.
SchwartzBD, MatousovaE, WhiteR, BanwellMG, WillisAC. (2013) A chemoenzymatic total synthesis of the protoilludane aryl ester (+)-armillarivin. Organic Letters, 15, 1934–1937.
64.
SchmidRD, VergerR. (1998) Lipases: interfacial enzymes with attractive applications. Angewandte Chemie International Edition, 37, 1608–1633.
65.
SerraS. (2011) Lipase-mediated resolution of substituted 2-aryl-propanols: application to the enantioselective synthesis of phenolic sesquiterpenes. Tetrahedron: Asymmetry, 22, 619–628.
66.
SerraS, FronzaG. (2012) Unambiguous characterization of the sesquiterpene (7R,9E)-1,2,11-trihydroxy-1,3,5,9-bisabolatetraene through Its enantioselective synthesis. European Journal of Organic Chemistry, 4838–4843.
67.
SerraS. (2014) Preparation and use of enantioenriched 2-aryl-propylsulfonylbenzene derivatives as valuable building blocks for the enantioselective synthesis of bisabolane sesquiterpenes. Tetrahedron: Asymmetry, 25, 1561–1572
68.
SerraS. (2013) Enantioselective synthesis of natural trinorsesquiterpene tetralones by chemo-enzymatic approaches. Natural Product Communications, 8, 863–868.
69.
TanikawaS, OnoM, AkitaH. (2005) Enzymatic resolution of (+/-)-5-acetoxy-4-aryl-(2E)-pentenoate derivatives. Chemical & Pharmaceutical Bulletin, 53, 565–569.
70.
OnoM, SuzukiK, TanikawaS, AkitaH. (2001) First synthesis of (+)- and (-)-elvirol based on an enzymatic function. Tetrahedron: Asymmetry, 12, 2597–2604.
71.
OnoM, OguraY, HatogaiK, AkitaH. (1995) Total synthesis of (S)-(+)-curcudiol, (S)- and (R)-(-)-curcuphenol based on enzymatic resolution of a primary alcohol possessing one stereogenic center. Tetrahedron: Asymmetry, 6, 1829–1832.
72.
FujiiM, IshiiS, SaitoR, AkitaH. (2009) Enzymatic resolution of albicanol and its application to the synthesis of (-)-copalic acid. Journal of Molecular Catalysis B: Enzymatic, 59, 254–260.
73.
KawasakiM, HayashiY, KakudaH, ToyookaN, TanakaA, GotoM, KawabataS, KometaniT. (2005) Asymmetric synthesis of 5,6-dehydrosenedigitalene using lipase-catalyzed highly enantioselective transesterification of a primary alcohol with vinyl 3-(4-trifluoromethylphenyl)propanoate. Tetrahedron: Asymmetry, 16, 4065–4072.
74.
KamalA, MalikMS, ShaikAA, AzeezaS. (2007) Enantioselective synthesis of (R)- and (S)-curcumene and curcuphenol: an efficient chemoenzymatic route. Tetrahedron: Asymmetry, 18, 2547–2553.
75.
KamalA, Shaheer MalikM, AzeezaS, BajeeS, ShaikAA. (2009) Total synthesis of (R)- and (S)-turmerone and (7S,9R)-bisacumol by an efficient chemoenzymatic approach. Tetrahedron: Asymmetry, 20, 1267–1271.
76.
Garcia-UrdialesE, AlfonsoI, GotorV. (2005) Enantioselective enzymatic desymmetrizations in organic synthesis. Chemical Reviews, 105, 313–354.
77.
FujitaT, TanakaM, NorimineY, SuemuneH, SakaiK. (1997) Enantioselective synthesis of (-)-curcumanolide A using enzymatic transesterification of meso-spirodiol. The Journal of Organic Chemistry, 62, 3824–3830.
78.
CanetJL, FadelA, SalaunJ. (1992) Asymmetric construction of quaternary carbons from chiral malonates: selective and versatile total syntheses of the enantiomers of alpha- and beta-cuparenones from a common optically active precursor. The Journal of Organic Chemistry, 57, 3463–3473.
79.
KosakaT, BandoT, ShishidoK. (1997) New asymmetric construction of the benzylic quaternary stereogenic centre: an enantiocontrolled access to (-)-α-cuparenone. Chemical Communications, 1167–1168.
80.
KishukuH, ShindoM, ShishidoK. (2003) Enantioselective total synthesis of (-)-heliannuol A. Chemical Communications, 350–351.
81.
NakashimaH, SatoM, TaniguchiT, OgasawaraK. (2000) An enantiodivergent route to α-cuparenone utilizing chiral cyclopentenol having a latent meso structure. Tetrahedron Letters, 41, 2639–2642.
82.
SerraS, FugantiC, BrennaE. (2006) Synthesis, olfactory evaluation, and determination of the absolute configuration of the 3,4-didehydroionone stereoisomers. Helvetica Chimica Acta, 89, 1110–1122
83.
SerraS. (2013) An expedient preparation of enantio-enriched ambergris odorants starting from commercial ionone alpha. Flavour and Fragrance Journal, 28, 46–52.
84.
SerraS. (2012) A practical, enantiospecific synthesis of (S)-trans-γ-monocyclofarnesol. Natural Product Communications, 7, 1569–1572.
85.
SerraS, CominettiAA, LissoniV. (2014) A general synthetic approach to hydroquinone meroterpenoids: Stereoselective synthesis of (+)-(S)-metachromin V and alliodorol. Natural Product Communications, 9, 303–308
86.
SerraS, CominettiAA, LissoniV. (2014) Use of (S)-trans-γ-monocyclofarnesol as a useful chiral building block for the stereoselective synthesis of diterpenic natural products. Natural Product Communications, 9, 329–335.
87.
TakikawaH, UedaK, SasakiM. (2004) The first synthesis and absolute configuration of glaucescenolide. Tetrahedron Letters, 45, 5569–5571.
88.
AcherarS, AudranG, VanthuyneN, MontiH. (2003) Use of lipase-catalyzed kinetic resolution for the enantioselective approach toward sesquiterpenes containing quaternary centers: the cuparane family. Tetrahedron: Asymmetry, 14, 2413–2418
89.
AcherarS, AudranG, CecchinF, MontiH. (2004) Enantioselective synthesis of natural (-)-tochuinyl acetate, (-)-dihydrotochuinyl acetate and (+)-β-cuparenone using both enantiomers of the same building block. Tetrahedron, 60, 5907–5912.
90.
LordMD, NegriJT, PaquetteLA. (1995) Oxonium ion-initiated pinacolic ring expansion reactions. Application to the enantioselective synthesis of the spirocyclic sesquiterpene ethers dactyloxene-B and -C. The Journal of Organic Chemistry, 60, 191–195.
91.
MehtaG, SrinivasK. (2001) Enantioselective total syntheses of the novel tricyclic sesquiterpene hydrocarbons (+)- and (-)-kelsoene. Absolute configuration of the natural product. Tetrahedron Letters, 42, 2855–2857.
92.
BrennaE, FugantiC, GrasselliP, SerraS. (2001) Enzyme-mediated synthesis of (S)- and (R)-verapamil. European Journal of Organic Chemistry, 1349–1357
93.
BrennaE, Dei NegriC, FugantiC, GattiFG, SerraS. (2004) Enantioselective synthesis of cis-7-methoxy-calamenene via Claisen rearrangement of an enzymatically resolved allyl alcohol. Tetrahedron: Asymmetry, 15, 335–340.
