Skip to main content

Microbial Production of Isoprenoids

  • 1075 Accesses

Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)

Abstract

Isoprenoids are among the most diverse groups of compounds synthesized by biological systems; it has been estimated that there are approximately 30,000–50,000 known isoprenoids, which include the terpenoids and carotenoids. Isoprenoids are important in maintaining membrane fluidity, electron transport, protein prenylation, and cellular and organismal development and in controlling pests. Many isoprenoids have found application as fragrances and essential oils, pharmaceuticals, specialty and commodity chemicals, and most recently biofuels. To make all of these applications of isoprenoids possible, their production in microbial hosts is essential. Recently, there has been much progress in producing these complex hydrocarbons in both Escherichia coli and Saccharomyces cerevisiae. In this chapter, we review recent progress in this area.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-50436-0_219
  • Chapter length: 24 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   399.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-50436-0
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Hardcover Book
USD   499.99
Price excludes VAT (USA)
Fig. 1
Fig. 2
Fig. 3

References

  • Ajikumar PK et al (2010) Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia Coli. Science (New York) 330(6000):70–74

    CAS  CrossRef  Google Scholar 

  • Albertsen L et al (2011) Diversion of flux toward sesquiterpene production in saccharomyces cerevisiae by fusion of host and heterologous enzymes. Appl Environ Microbiol 77(3):1033–1040

    CAS  PubMed  CrossRef  Google Scholar 

  • Alonso-Gutierrez J et al (2013) Metabolic engineering of Escherichia Coli for limonene and perillyl alcohol production. Metab Eng 19:33–41

    CAS  PubMed  CrossRef  Google Scholar 

  • Alonso-Gutierrez J et al (2015) Principal Component Analysis of Proteomics (PCAP) as a tool to direct metabolic engineering. Metab Eng 28:123–133

    CAS  PubMed  CrossRef  Google Scholar 

  • Andersen-Ranberg J et al (2016) Expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis. Angew Chem 55(6):2142–2146

    CAS  CrossRef  Google Scholar 

  • Anthony JR et al (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia Coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11(1):13–19

    CAS  PubMed  CrossRef  Google Scholar 

  • Beller HR, Lee TS, Katz L (2015) Natural products as biofuels and bio-based chemicals: fatty acids and isoprenoids. Nat Prod Rep 32(10):1508–1526

    CAS  PubMed  CrossRef  Google Scholar 

  • Bertea CM, Schalk M, Karp F, Maffei M, Croteau R (2001) Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P450 monooxygenase: cloning, functional expression, and characterization of the responsible gene. Arch Biochem Biophys 390(2):279–286

    CAS  PubMed  CrossRef  Google Scholar 

  • Biggs BW et al (2016) Overcoming heterologous protein interdependency to optimize P450-mediated taxol precursor synthesis in Escherichia Coli. Proc Natl Acad Sci U S A 113(12):3209–3214

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Blumberg PM (1988) Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth rhoads memorial award lecture. Cancer Res 48(1):1–8

    CAS  PubMed  Google Scholar 

  • Bromann K, Toivari M, Viljanen K, Ruohonen L, Nakari-Setälä T (2016) Engineering aspergillus nidulans for heterologous ent-kaurene and gamma-terpinene production. Appl Microbiol Biotechnol 100(14):6345–6359

    CAS  PubMed  CrossRef  Google Scholar 

  • Campos N et al (2001) Escherichia Coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate: a novel system for the genetic analysis of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. Biochem J 353(Pt 1):59–67

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Cankar K et al (2011) A chicory cytochrome P450 mono-oxygenase CYP71AV8 for the oxidation of (+)-valencene. FEBS Lett 585(1):178–182

    CAS  PubMed  CrossRef  Google Scholar 

  • Cann AF, Liao JC (2010) Pentanol isomer synthesis in engineered microorganisms. Appl Microbiol Biotechnol 85(4):893–899

    CAS  PubMed  CrossRef  Google Scholar 

  • Carter OA, Peters RJ, Croteau R (2003) Monoterpene biosynthesis pathway construction in Escherichia Coli. Phytochemistry 64(2):425–433

    CAS  PubMed  CrossRef  Google Scholar 

  • Chandran SS, Kealey JT, Reeves CD (2011) Microbial production of isoprenoids. Process Biochem 46(9):1703–1710

    CAS  CrossRef  Google Scholar 

  • Chang MCY, Eachus RA, Trieu W, Ro D-K, Keasling JD (2007) Engineering Escherichia coli for production of functionalized terpenoids using plant P450s. Nat Chem Biol 3(5):274–277

    CAS  PubMed  CrossRef  Google Scholar 

  • Chappell J (1995) Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Annu Rev Plant Physiol Plant Mol Biol 46(1):521–547

    CAS  CrossRef  Google Scholar 

  • Chiba R, Minami A, Gomi K, Oikawa H (2013) Identification of ophiobolin F synthase by a genome mining approach: a sesterterpene synthase from Aspergillus clavatus. Org Lett 15(3):594–597

    CAS  PubMed  CrossRef  Google Scholar 

  • Chubukov V et al (2015) Acute limonene toxicity in Escherichia coli is caused by limonene hydroperoxide and alleviated by a point mutation in alkyl hydroperoxidase AhpC. Appl Environ Microbiol 81(14):4690–4696

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Chuck CJ, Donnelly J (2014) The compatibility of potential bioderived fuels with jet A-1 aviation kerosene. Appl Energy 118:83–91

    CAS  CrossRef  Google Scholar 

  • Collu G et al (2001) Geraniol 10-hydroxylase1, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett 508(2):215–220

    CAS  PubMed  CrossRef  Google Scholar 

  • Croteau R, Ketchum REB, Long RM, Kaspera R, Wildung MR (2006) Taxol biosynthesis and molecular genetics. Phytochem Rev Proc Phytochem Soc Eur 5(1):75–97

    CAS  CrossRef  Google Scholar 

  • Cuellar MC, Heijnen JJ, van der Wielen LAM (2013) Large-scale production of diesel-like biofuels – process design as an inherent part of microorganism development. Biotechnol J 8(6):682–689

    CAS  PubMed  CrossRef  Google Scholar 

  • Cui L, Su X-z S (2009) Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti-Infect Ther 7(8):999–1013

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Cusidó RM et al (1999) Production of taxol® and baccatin III by a selected taxus baccata callus line and its derived cell suspension culture. Plant Sci 146(2):101–107

    CrossRef  Google Scholar 

  • Davies FK, Work VH, Beliaev AS, Posewitz MC (2014) Engineering limonene and bisabolene production in wild type and a glycogen-deficient mutant of Synechococcus sp. Pcc 7002. Front Bioeng Biotechnol 2:21

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Dejong JHM et al (2006) Genetic engineering of taxol biosynthetic genes in Saccharomyces cerevisiae. Biotechnol Bioeng 93(2):212–224

    CAS  PubMed  CrossRef  Google Scholar 

  • Dickschat JS (2016) Bacterial terpene cyclases. Nat Prod Rep 33(1):87–110

    CAS  PubMed  CrossRef  Google Scholar 

  • Ding M-Z et al (2014) Biosynthesis of taxadiene in Saccharomyces cerevisiae: selection of geranylgeranyl diphosphate synthase directed by a computer-aided docking strategy. PLoS ONE 9(10):e109348

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Eisenreich W et al (1998) The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chem Biol 5(9):221–233

    CrossRef  Google Scholar 

  • Engels B, Dahm P, Jennewein S (2008) Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards taxol (Paclitaxel) production. Metab Eng 10(3–4):201–206

    CAS  PubMed  CrossRef  Google Scholar 

  • Formighieri C, Melis A (2014) Carbon partitioning to the terpenoid biosynthetic pathway enables heterologous β-phellandrene production in Escherichia coli cultures. Arch Microbiol 196(12):853–861

    CAS  PubMed  CrossRef  Google Scholar 

  • Fortman JL et al (2008) Biofuel alternatives to ethanol: pumping the microbial well. Trends Biotechnol 26(7):375–381

    CAS  PubMed  CrossRef  Google Scholar 

  • Fraga BM (2005) Natural sesquiterpenoids. Nat Prod Rep 22(4):465–486

    CAS  PubMed  CrossRef  Google Scholar 

  • Gelb MH et al (1995) The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol. Cancer Lett 91(2):169–175

    CAS  PubMed  CrossRef  Google Scholar 

  • George KW, Thompson MG et al (2015a) Metabolic engineering for the high-yield production of isoprenoid-based c5 alcohols in E. coli. Sci Rep 5:11128

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • George KW, Alonso-Gutierrez J, Keasling JD, Lee TS (2015b) Isoprenoid drugs, biofuels, and chemicals – artemisinin, farnesene, and beyond. Adv Biochem Eng Biotechnol 148:355–389

    CAS  PubMed  Google Scholar 

  • Góngora-Castillo E et al (2012) Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. PLoS ONE 7(12):e52506

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Gould MN (1997) Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect 105(4):977–979

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Hahn FM, Poulter CD (1995) Isolation of schizosaccharomyces pombe isopentenyl diphosphate isomerase cDNA clones by complementation and synthesis of the enzyme in Escherichia coli. J Biol Chem 270(19):11298–11303

    CAS  PubMed  CrossRef  Google Scholar 

  • Halaweish FT, Kronberg S, Hubert MB, Rice JA (2002) Toxic and aversive diterpenes of Euphorbia esula. J Chem Ecol 28(8):1599–1611

    CAS  PubMed  CrossRef  Google Scholar 

  • Hamberger B, Bak S (2013) Plant p450s as versatile drivers for evolution of species-specific chemical diversity. Philos Trans R Soc Lond Ser B Biol Sci 368(1612):20120426

    CrossRef  CAS  Google Scholar 

  • Hamberger B, Ohnishi T, Hamberger B, Séguin A, Bohlmann J (2011) Evolution of diterpene metabolism: sitka spruce cyp720b4 catalyzes multiple oxidations in resin acid biosynthesis of conifer defense against insects. Plant Physiol 157(4):1677–1695

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Hampton RY, Garza RM (2009) Protein quality control as a strategy for cellular regulation: lessons from ubiquitin-mediated regulation of the sterol pathway. Chem Rev 109(4):1561–1574

    CAS  PubMed  CrossRef  Google Scholar 

  • Hampton R, Dimster-Denk D, Rine J (1996) The biology of HMG-CoA reductase: the pros of contra-regulation. Trends Biochem Sci 21(4):140–145

    CAS  PubMed  CrossRef  Google Scholar 

  • Harvey BG, Wright ME, Quintana RL (2010) High-density renewable fuels based on the selective dimerization of pinenes. Energy Fuels Am Chem Soc J 24(1):267–273

    CAS  CrossRef  Google Scholar 

  • Haudenschild C, Schalk M, Karp F, Croteau R (2000) Functional expression of regiospecific cytochrome P450 limonene hydroxylases from mint (Mentha spp.) in Escherichia coli and Saccharomyces cerevisiae. Arch Biochem Biophys 379(1):127–136

    CAS  PubMed  CrossRef  Google Scholar 

  • Hefner J et al (1996) Cytochrome P450-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5a-o1: the first oxygenation step in taxol biosynthesis. Chem Biol 3(6):479–489

    CAS  PubMed  CrossRef  Google Scholar 

  • Hellier P, Al-Haj L, Talibi M, Purton S, Ladommatos N (2013) Combustion and emissions characterization of terpenes with a view to their biological production in Cyanobacteria. Fuel 111:670–688

    CAS  CrossRef  Google Scholar 

  • Hohl RJ (1996) Monoterpenes as regulators of malignant cell proliferation. Adv Exp Med Biol 401:137–146

    CAS  PubMed  CrossRef  Google Scholar 

  • Horton CE, Huang K-X, Bennett GN, Rudolph FB (2003) Heterologous expression of the Saccharomyces cerevisiae alcohol acetyltransferase genes in Clostridium acetobutylicum and Escherichia coli for the production of isoamyl acetate. J Ind Microbiol Biotechnol 30(7):427–432

    CAS  PubMed  CrossRef  Google Scholar 

  • Horwitz AA et al (2015) Efficient multiplexed integration of synergistic alleles and metabolic pathways in yeasts via CRISPR-cas. Cell Syst 1(1):88–96

    CAS  PubMed  CrossRef  Google Scholar 

  • Huang KX, Huang QL, Wildung MR, Croteau R, Scott AI (1998) Overproduction, in Escherichia coli, of soluble taxadiene synthase, a key enzyme in the taxol biosynthetic pathway. Protein Expr Purif 13(1):90–96

    CAS  PubMed  CrossRef  Google Scholar 

  • Hull A, Golubkov I, Kronberg B, Marandzheva T, van Stam J (2006) An alternative fuel for spark ignition engines. Int J Eng Res 7(3):203–214

    CAS  CrossRef  Google Scholar 

  • Ignea C, Pontini M, Maffei ME, Makris AM, Kampranis SC (2014) Engineering monoterpene production in yeast using a synthetic dominant negative geranyl diphosphate synthase. ACS Synth Biol [Electron Resour] 3(5):298–306

    CAS  CrossRef  Google Scholar 

  • Ignea C et al (2015) Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase. Metab Eng 27:65–75

    CAS  PubMed  CrossRef  Google Scholar 

  • Ignea C et al (2016) Carnosic acid biosynthesis elucidated by a synthetic biology platform. Proc Natl Acad Sci U S A 113(13):3681–3686

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Jennewein S, Croteau R (2001) Taxol: biosynthesis, molecular genetics, and biotechnological applications. Appl Microbiol Biotechnol 57(1–2):13–19

    CAS  PubMed  Google Scholar 

  • Jiao W, Dong W, Li Z, Deng M, Runhua L (2009) Lathyrane diterpenes from Euphorbia lathyris as modulators of multidrug resistance and their crystal structures. Bioorg Med Chem 17(13):4786–4792

    CAS  PubMed  CrossRef  Google Scholar 

  • Kang M-K, Eom J-H, Kim Y, Um Y, Woo HM (2014) Biosynthesis of pinene from glucose using metabolically-engineered Corynebacterium glutamicum. Biotechnol Lett 36(10):2069–2077

    CAS  PubMed  CrossRef  Google Scholar 

  • Kaspera R, Croteau R (2006) Cytochrome P450 oxygenases of taxol biosynthesis. Phytochem Rev Proc Phytochem Soc Eur 5(2–3):433–444

    CAS  CrossRef  Google Scholar 

  • Kim E-M, Eom J-H, Um Y, Kim Y, Woo HM (2015) Microbial synthesis of myrcene by metabolically engineered Escherichia coli. J Agric Food Chem 63(18):4606–4612

    CAS  PubMed  CrossRef  Google Scholar 

  • King AJ et al (2016) A cytochrome P450-mediated intramolecular carbon-carbon ring closure in the biosynthesis of multidrug-resistance-reversing lathyrane diterpenoids. Chembiochem 17(17):1593–1597

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Kirby J, Keasling JD (2009) Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol 60:335–355

    CAS  PubMed  CrossRef  Google Scholar 

  • Kirby J et al (2010) Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae. Phytochemistry 71(13):1466–1473

    CAS  PubMed  CrossRef  Google Scholar 

  • Kiyota H, Okuda Y, Ito M, Hirai MY, Ikeuchi M (2014) Engineering of Cyanobacteria for the photosynthetic production of limonene from CO2. J Biotechnol 185:1–7

    CAS  PubMed  CrossRef  Google Scholar 

  • Köllner TG, Gershenzon J, Degenhardt J (2009) Molecular and biochemical evolution of maize terpene synthase 10, an enzyme of indirect defense. Phytochemistry 70(9):1139–1145

    PubMed  CrossRef  CAS  Google Scholar 

  • Kung Y et al (2014) Constructing tailored isoprenoid products by structure-guided modification of geranylgeranyl reductase. Structure 22(7):1028–1036

    CAS  PubMed  CrossRef  Google Scholar 

  • Lange BM, Rujan T, Martin W, Croteau R (2000) Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes. Proc Natl Acad Sci U S A 97(24):13172–13177

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Lee ME, DeLoache WC, Cervantes B, Dueber JE (2015) A highly characterized yeast toolkit for modular, multipart assembly. ACS Synth Biol [Electron Resour] 4(9):975–986.

    Google Scholar 

  • Leipoldt F et al (2015) Diversity of ABBA prenyltransferases in marine Streptomyces sp. CNQ-509: promiscuous enzymes for the biosynthesis of mixed terpenoid compounds. PLoS ONE 10(12):e0143237

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Liao P, Hemmerlin A, Bach TJ, Chye M-L (2016) The potential of the mevalonate pathway for enhanced isoprenoid production. Biotechnol Adv 34(5):697–713

    CAS  PubMed  CrossRef  Google Scholar 

  • Lindberg P, Park S, Melis A (2010) Engineering a platform for photosynthetic isoprene production in Cyanobacteria, using Synechocystis as the model organism. Metab Eng 12(1):70–79

    CAS  PubMed  CrossRef  Google Scholar 

  • Lois LM et al (1998) Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc Natl Acad Sci U S A 95(5):2105–2110

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Lubertozzi D, Keasling JD (2008) Expression of a synthetic artemesia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribution. J Ind Microbiol Biotechnol 35(10):1191–1198

    CAS  PubMed  CrossRef  Google Scholar 

  • Luo P, Wang YH, Wang GD, Essenberg M, Chen XY (2001) Molecular cloning and functional identification of (+)-delta-cadinene-8-hydroxylase, a cytochrome P450 mono-oxygenase (CYP706B1) of cotton sesquiterpene biosynthesis. Plant J Cell Mol Biol 28(1):95–104

    CAS  CrossRef  Google Scholar 

  • Luo D et al (2016) Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L. Proc Natl Acad Sci U S A 113(34):5082–5089

    CrossRef  CAS  Google Scholar 

  • Lupien S, Karp F, Ponnamperuma K, Wildung M, Croteau R (1995) Cytochrome P450 limonene hydroxylases of Mentha species. Drug Metabol Drug Interact 12(3–4):245–260

    CAS  PubMed  Google Scholar 

  • Mack JH, Rapp VH, Broeckelmann M, Lee TS, Dibble RW (2014) Investigation of biofuels from microorganism metabolism for use as anti-knock additives. Fuel 117:939–943

    CAS  CrossRef  Google Scholar 

  • Martin VJJ, Yoshikuni Y, Keasling JD (2001) The in vivo synthesis of plant sesquiterpenes by Escherichia coli. J Biochem Microbiol Technol Eng 75(5):497–503

    CAS  Google Scholar 

  • Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol 21(7):796–802

    CAS  PubMed  CrossRef  Google Scholar 

  • Martin DM, Fäldt J, Bohlmann J (2004) Functional characterization of nine norway spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-D subfamily. Plant Physiol 135(4):1908–1927

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Marwick C (2005) Researchers investigate potential use of plant as a pain killer. BMJ (Clin Res Ed) 331(7525):1104

    CrossRef  Google Scholar 

  • McCaskill D, Croteau R (1997) Prospects for the bioengineering of isoprenoid biosynthesis. Adv Biochem Eng Biotechnol 55:107–146

    CAS  PubMed  Google Scholar 

  • McGarvey DJ, Croteau R (1995) Terpenoid metabolism. Plant Cell 7(7):1015–1026

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Meadows AL et al (2016) Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature 537(7622):694–697

    CAS  PubMed  CrossRef  Google Scholar 

  • Meigs TE, Roseman DS, Simoni RD (1996) Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation by the nonsterol mevalonate metabolite farnesol in vivo. J Biol Chem 271(14):7916–7922

    CAS  PubMed  CrossRef  Google Scholar 

  • Melillo E, Setroikromo R, Quax WJ, Kayser O (2013) Production of α-cuprenene in xanthophyllomyces dendrorhous: a step closer to a potent terpene biofactory. Microb Cell Factories 12:13

    CAS  CrossRef  Google Scholar 

  • Mercke P, Crock J, Croteau R, Brodelius PE (1999) Cloning, expression, and characterization of epi-cedrol synthase, a sesquiterpene cyclase from Artemisia annua L. Arch Biochem Biophys 369(2):213–222

    CAS  PubMed  CrossRef  Google Scholar 

  • Mercke P, Bengtsson M, Bouwmeester HJ, Posthumus MA, Brodelius PE (2000) Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch Biochem Biophys 381(2):173–180

    CAS  PubMed  CrossRef  Google Scholar 

  • Meylemans HA, Quintana RL, Goldsmith BR, Harvey BG (2011) Solvent-free conversion of linalool to methylcyclopentadiene dimers: a route to renewable high-density fuels. ChemSusChem 4(4):465–469

    CAS  PubMed  CrossRef  Google Scholar 

  • Meylemans HA, Quintana RL, Harvey BG (2012) Efficient conversion of pure and mixed terpene feedstocks to high density fuels. Fuel 97:560–568

    CAS  CrossRef  Google Scholar 

  • Mi J, Schewe H, Buchhaupt M, Holtmann D, Schrader J (2016) Efficient hydroxylation of 1,8-cineole with monoterpenoid-resistant recombinant Pseudomonas putida GS1. World J Microbiol Biotechnol 32(7):112

    PubMed  CrossRef  CAS  Google Scholar 

  • Narita K, Ohnuma S, Nishino T (1999) Protein design of geranyl diphosphate synthase. Structural features that define the product specificities of prenyltransferases. J Biochem 126(3):566–571

    CAS  PubMed  CrossRef  Google Scholar 

  • Newman JD et al (2006) High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli. Biotechnol Bioeng 95(4):684–691

    CAS  PubMed  CrossRef  Google Scholar 

  • O’Connor SE, Maresh JJ (2006) Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat Prod Rep 23(4):532–547

    PubMed  CrossRef  CAS  Google Scholar 

  • Ohnuma S et al (1996) Conversion from farnesyl diphosphate synthase to geranylgeranyl diphosphate synthase by random chemical mutagenesis. J Biol Chem 271(17):10087–10095

    CAS  PubMed  CrossRef  Google Scholar 

  • Okamoto S et al (2011) A short-chain dehydrogenase involved in terpene metabolism from Zingiber zerumbet. FEBS J 278(16):2892–2900

    CAS  PubMed  CrossRef  Google Scholar 

  • Ozaki T, Zhao P, Shinada T, Nishiyama M, Kuzuyama T (2014) Cyclolavandulyl skeleton biosynthesis via both condensation and cyclization catalyzed by an unprecedented member of the cis-isoprenyl diphosphate synthase superfamily. J Am Chem Soc 136(13):4837–4840

    CAS  PubMed  CrossRef  Google Scholar 

  • Özaydın B, Burd H, Lee TS, Keasling JD (2013) Carotenoid-based phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production. Metab Eng 15:174–183

    PubMed  CrossRef  CAS  Google Scholar 

  • Paddon CJ et al (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496(7446):528–532

    CAS  PubMed  CrossRef  Google Scholar 

  • Peralta-Yahya PP, Keasling JD (2010) Advanced biofuel production in microbes. Biotechnol J 5(2):147–162

    CAS  PubMed  CrossRef  Google Scholar 

  • Peralta-Yahya PP et al (2011) Identification and microbial production of a terpene-based advanced biofuel. Nat Commun 2:483

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Peralta-Yahya PP, Zhang F, del Cardayre SB, Keasling JD (2012) Microbial engineering for the production of advanced biofuels. Nature 488(7411):320–328

    CAS  PubMed  CrossRef  Google Scholar 

  • Phelan RM, Sekurova ON, Keasling JD, Zotchev SB (2015) Engineering terpene biosynthesis in streptomyces for production of the advanced biofuel precursor bisabolene. ACS Synth Biol [Electron Resour] 4(4):393–399

    CAS  CrossRef  Google Scholar 

  • Phulara SC, Chaturvedi P, Gupta P (2016) Isoprenoid-based biofuels: homologous expression and heterologous expression in prokaryotes. Appl Environ Microbiol 82(19):5730–5740

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Picaud S, Brodelius M, Brodelius PE (2005) Expression, purification and characterization of recombinant (E)-beta-farnesene synthase from Artemisia annua. Phytochemistry 66(9):961–967

    CAS  PubMed  CrossRef  Google Scholar 

  • Pitera DJ, Paddon CJ, Newman JD, Keasling JD (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng 9(2):193–207

    CAS  PubMed  CrossRef  Google Scholar 

  • Potter D, Miziorko HM (1997) Identification of catalytic residues in human mevalonate kinase. J Biol Chem 272(41):25449–25454

    CAS  PubMed  CrossRef  Google Scholar 

  • Ralston L et al (2001) Cloning, heterologous expression, and functional characterization of 5-epi-aristolochene-1,3-dihydroxylase from tobacco (Nicotiana tabacum). Arch Biochem Biophys 393(2):222–235

    CAS  PubMed  CrossRef  Google Scholar 

  • Reiling KK et al (2004) Mono and diterpene production in Escherichia coli. Biotechnol Bioeng 87(2):200–212

    CAS  PubMed  CrossRef  Google Scholar 

  • Reinsvold RE, Jinkerson RE, Radakovits R, Posewitz MC, Basu C (2011) The production of the sesquiterpene β-caryophyllene in a transgenic strain of the Cyanobacterium Synechocystis. J Plant Physiol 168(8):848–852

    CAS  PubMed  CrossRef  Google Scholar 

  • Renninger N, McPhee D (2008) Fuel compositions comprising farnesane and farnesane derivatives and method of making and using same. US Patent 20,080,098,645

    Google Scholar 

  • Ro D-K et al (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440(7086):940–943

    CAS  PubMed  CrossRef  Google Scholar 

  • Rohmer M, Knani M, Simonin P, Sutter B, Sahm H (1993) Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem J 295(Pt 2):517–524

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Roth RJ, Acton N (1989) A simple conversion of artemisinic acid into artemisinin. J Nat Prod 52(5):1183–1185

    CAS  PubMed  CrossRef  Google Scholar 

  • Rude MA, Schirmer A (2009) New microbial fuels: a biotech perspective. Curr Opin Microbiol 12(3):274–281

    CAS  PubMed  CrossRef  Google Scholar 

  • Ryder JA (2009) Jet fuel compositions. US Patent 7,589,243

    Google Scholar 

  • Sarria S, Wong B, Martín HG, Keasling JD, Peralta-Yahya P (2014) Microbial synthesis of pinene. ACS Synth Biol [Electron Resour] 3(7):466–475

    CAS  CrossRef  Google Scholar 

  • Schalk M, Croteau R (2000) A single amino acid substitution (F363I) converts the regiochemistry of the spearmint (−)-limonene hydroxylase from a C6- to a C3-hydroxylase. Proc Natl Acad Sci U S A 97(22):11948–11953

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Schoendorf A, Rithner CD, Williams RM, Croteau RB (2001) Molecular cloning of a cytochrome P450 taxane 10 beta-hydroxylase cDNA from taxus and functional expression in yeast. Proc Natl Acad Sci U S A 98(4):1501–1506

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Schwender J, Seemann M, Lichtenthaler HK, Rohmer M (1996) Biosynthesis of isoprenoids (carotenoids, sterols, prenyl side-chains of chlorophylls and plastoquinone) via a novel pyruvate/glyceraldehyde 3-phosphate non-mevalonate pathway in the green alga Scenedesmus obliquus. Biochem J 316(1):73–80

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Singh R, Vadlani PV, Harrison ML, Bennett GN, San KY (2008) Aerobic production of isoamyl acetate by overexpression of the yeast alcohol acetyl-transferases AFT1 and AFT2 in Escherichia coli and using low-cost fermentation ingredients. Bioprocess Biosyst Eng 31(4):299–306

    CAS  PubMed  CrossRef  Google Scholar 

  • Skeel RT, Khleif SN (eds) (2011) Handbook of cancer chemotherapy. Illustrated. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Srivalli KMR, Lakshmi PK (2012) Overview of P-glycoprotein inhibitors: a rational outlook. Braz J Pharm Sci 48(3):353–367

    CAS  CrossRef  Google Scholar 

  • Steele CL, Crock J, Bohlmann J, Croteau R (1998) Sesquiterpene synthases from Grand Fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of delta-selinene synthase and gamma-humulene synthase. J Biol Chem 273(4):2078–2089

    CAS  PubMed  CrossRef  Google Scholar 

  • Szkopińska A, Swiezewska E, Karst F (2000) The regulation of activity of main mevalonic acid pathway enzymes: farnesyl diphosphate synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, and squalene synthase in yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun 267(1):473–477

    PubMed  CrossRef  CAS  Google Scholar 

  • Takahashi S, Kuzuyama T, Seto H (1999) Purification, characterization, and cloning of a eubacterial 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme involved in biosynthesis of terpenoids. J Bacteriol 181(4):1256–1263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi S et al (2007) Functional characterization of premnaspirodiene oxygenase, a cytochrome P450 catalyzing regio- and stereo-specific hydroxylations of diverse sesquiterpene substrates. J Biol Chem 282(43):31744–31754

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Takase H et al (2016) Cytochrome P450 CYP71BE5 in grapevine (Vitis vinifera) catalyzes the formation of the spicy aroma compound (−)-rotundone. J Exp Bot 67(3):787–798

    CAS  PubMed  CrossRef  Google Scholar 

  • Tarshis LC, Mujing Y, Dale Poulter C, Sacchettini JC (1994) Crystal structure of recombinant farnesyl diphosphate synthase at 2.6-.ANG. Resolution. Biochemistry 33(36):10871–10877

    CAS  PubMed  CrossRef  Google Scholar 

  • Tracy NI, Chen D, Crunkleton DW, Price GL (2009) Hydrogenated monoterpenes as diesel fuel additives. Fuel 88(11):2238–2240

    CAS  CrossRef  Google Scholar 

  • Trikka FA et al (2015) Iterative carotenogenic screens identify combinations of yeast gene deletions that enhance sclareol production. Microb Cell Factories 14:60

    CrossRef  CAS  Google Scholar 

  • Tsuruta H et al (2009) High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS ONE 4(2):e4489

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Unterweger B et al (2016) Characterisation of CYP101J2, CYP101J3 and CYP101J4, Three 1,8-cineole-hydroxylating cytochrome P450 monooxygenases from sphingobium yanoikuyae strain B2. Appl Environ Microbiol 82(22):6507–6517

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Vasas A, Hohmann J (2014) Euphorbia diterpenes: isolation, structure, biological activity, and synthesis (2008–2012). Chem Rev 114(17):8579–8612

    CAS  PubMed  CrossRef  Google Scholar 

  • Walker K, Croteau R (2001) Taxol biosynthetic genes. Phytochemistry 58(1):1–7

    CAS  PubMed  CrossRef  Google Scholar 

  • Wang K (2000) Isoprenyl diphosphate synthases. Biochim Biophys Acta (BBA) Mol Cell Biol Lipids 1529(1–3):33–48

    CAS  CrossRef  Google Scholar 

  • Wang Y-H, Essenberg M (2010) Inhibitor and substrate activities of sesquiterpene olefins toward +−δ-cadinene-8-hydroxylase, a cytochrome P450 monooxygenase (CYP706B1). Phytochemistry 71(16):1825–1831

    CAS  PubMed  CrossRef  Google Scholar 

  • Wang C, Yoon S-H et al (2011a) Metabolic engineering of Escherichia coli for α-farnesene production. Metab Eng 13(6):648–655

    CAS  PubMed  CrossRef  Google Scholar 

  • Wang C, Kim J-Y, Choi E-S, Kim S-W (2011b) Microbial production of farnesol (FOH): current states and beyond. Process Biochem 46(6):1221–1229

    CAS  CrossRef  Google Scholar 

  • Wang H, Zou Z, Wang S, Gong M (2013) Global analysis of transcriptome responses and gene expression profiles to cold stress of Jatropha curcas L. PLoS ONE 8(12):e82817

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Wang H-B, Wang X-Y, Liu L-P, Qin G-W, Kang T-G (2015) Tigliane diterpenoids from the Euphorbiaceae and Thymelaeaceae families. Chem Rev 115(9):2975–3011

    CAS  PubMed  CrossRef  Google Scholar 

  • Weaver LJ et al (2015) A kinetic-based approach to understanding heterologous mevalonate pathway function in E. coli. Biotechnol Bioeng 112(1):111–119

    CAS  PubMed  CrossRef  Google Scholar 

  • Westfall PJ et al (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci U S A 109(3):E111–E118

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Withers ST, Gottlieb SS, Lieu B, Newman JD, Keasling JD (2007) Identification of isopentenol biosynthetic genes from Bacillus subtilis by a screening method based on isoprenoid precursor toxicity. Appl Environ Microbiol 73(19):6277–6283

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Wriessnegger T et al (2014) Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. Metab Eng 24:18–29

    CAS  PubMed  CrossRef  Google Scholar 

  • Wüst M, Croteau RB (2002) Hydroxylation of specifically deuterated limonene enantiomers by cytochrome p450 limonene-6-hydroxylase reveals the mechanism of multiple product formation. Biochemistry 41(6):1820–1827

    PubMed  CrossRef  CAS  Google Scholar 

  • Yang Y, Dec JE, Dronniou N, Simmons B (2010) Characteristics of isopentanol as a fuel for HCCI engines. SAE Int J Fuels Lubr 3(2):725–741

    CAS  CrossRef  Google Scholar 

  • Yang J et al (2013) Metabolic engineering of Escherichia coli for the biosynthesis of alpha-Pinene. Biotechnol Biofuels 6(1):60

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Yang C et al (2016) Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli. Metab Eng 37:79–91

    CAS  PubMed  CrossRef  Google Scholar 

  • Yoshikuni Y, Ferrin TE, Keasling JD (2006) Designed divergent evolution of enzyme function. Nature 440(7087):1078–1082

    CAS  PubMed  CrossRef  Google Scholar 

  • Yu F et al (2011) Zingiber zerumbet CYP71BA1 catalyzes the conversion of α-humulene to 8-hydroxy-α-humulene in zerumbone biosynthesis. Cell Mol Life Sci 68(6):1033–1040

    CAS  PubMed  CrossRef  Google Scholar 

  • Zerbe P et al (2013) Gene discovery of modular diterpene metabolism in nonmodel systems. Plant Physiol 162(2):1073–1091

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  • Zhan X, Zhang Y-H, Chen D-F, Simonsen HT (2014) Metabolic engineering of the moss physcomitrella patens to produce the sesquiterpenoids patchoulol and α/β-santalene. Front Plant Sci 5:636

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Zhang H et al (2014) Microbial production of sabinene – a new terpene-based precursor of advanced biofuel. Microb Cell Factories 13:20

    CAS  CrossRef  Google Scholar 

  • Zhou K, Qiao K, Edgar S, Stephanopoulos G (2015) Distributing a metabolic pathway among a microbial consortium enhances production of natural products. Nat Biotechnol 33(4):377–383

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. D. Keasling .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2017 Springer International Publishing AG, part of Springer Nature

About this entry

Verify currency and authenticity via CrossMark

Cite this entry

Wong, J., Rios-Solis, L., Keasling, J.D. (2017). Microbial Production of Isoprenoids. In: Lee, S. (eds) Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids: Production of Fuels and Chemicals. Handbook of Hydrocarbon and Lipid Microbiology . Springer, Cham. https://doi.org/10.1007/978-3-319-50436-0_219

Download citation