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Microbial Production of Flavors and Fragrances

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Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids: Production of Fuels and Chemicals

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

Abstract

Synthetic biology opens a new door for sustainable and effective production of flavors and fragrances. It is achieved through the engineering of biosynthetic pathways for valuable compounds of interests in the microbial hosts such as Saccharomyces cerevisiae or Escherichia coli. This chapter focuses on the current state-of-art studies in pathway engineering for the production of functional isoprenoids , including monoterpenes and sesquiterpenes , as well as apocarotenoids . The relevant genetic manipulations on biosynthetic genes and enzymes performed in the last decade have been summarized. Various approaches, techniques to increase production titers of flavor compounds, and critical challenges have been highlighted and discussed in this chapter.

These authors contributed equally to this work.

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References

  • Albertsen L, Chen Y, Bach LS, Rattleff S, Maury J, Brix S, Nielsen J, Mortensen UH (2011) Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes. Appl Environ Microbiol 77:1033–1040

    Google Scholar 

  • Alonso-Gutierrez J, Chan R, Batth TS, Adams PD, Keasling JD, Petzold CJ, Lee TS (2013) Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production. Metab Eng 19:33–41

    Article  CAS  PubMed  Google Scholar 

  • Alonso-Gutierrez J, Kim EM, Batth TS, Cho N, Hu Q, Chan LJG, Petzold CJ, Hillson NJ, Adams PD, Keasling JD, Martin HG, Lee TS (2015) Principal component analysis of proteomics (PCAP) as a tool to direct metabolic engineering. Metab Eng 28:123–133

    Article  CAS  PubMed  Google Scholar 

  • Amiri P, Shahpiri A, Asadollahi MA, Momenbeik F, Partow S (2016) Metabolic engineering of Saccharomyces cerevisiae for linalool production. Biotechnol Lett 38:503–508

    Article  CAS  PubMed  Google Scholar 

  • Asadollahi MA, Maury J, MÞller K, Nielsen KF, Schalk M, Clark A, Nielsen J (2008) Production of plant sesquiterpenes in Saccharomyces cerevisiae: effect of ERG9 repression on sesquiterpene biosynthesis. Biotechnol Bioeng 99:666–677

    Article  CAS  PubMed  Google Scholar 

  • Bathaie SZ, Farajzade A, Hoshyar R (2014) A review of the chemistry and uses of crocins and crocetin, the carotenoid natural dyes in saffron, with particular emphasis on applications as colorants including their use as biological stains. Biotech Histochem 89:401–411

    Article  CAS  PubMed  Google Scholar 

  • Beekwilder J, van Rossum HM, Koopman F, Sonntag F, Buchhaupt M, Schrader J, Hall RD, Bosch D, Pronk JT, van Maris AJ, Daran JM (2014) Polycistronic expression of a β-carotene biosynthetic pathway in Saccharomyces cerevisiae coupled to β-ionone production. J Biotechnol 192B:383–392

    Article  Google Scholar 

  • Berger RG (2008) White biotechnology: sustainable options for the generation of natural volatile flavours. In: Expression of multidisciplinary. Flavour science. Proceedings of the 12th Weurman symposium, vol 1, pp 319–327

    Google Scholar 

  • Brennan TCR, Turner CD, Krömer JO, Nielsen LK (2012) Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae. Biotechnol Bioeng 109:2513–2522

    Article  CAS  PubMed  Google Scholar 

  • Brennan TC, Williams TC, Schulz BL, Palfreyman RW, Krömer JO, Nielsen LK (2015) Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae. Appl Environ Microbiol 81:3316–3325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brochado AR, Matos C, MÞller BL, Hansen J, Mortensen UH, Patil KR (2010) Improved vanillin production in baker’s yeast through in silico design. Microb Cell Factories 9:84

    Article  Google Scholar 

  • Carrau FM, Medina K, Boido E, Farina L, Gaggero C, Dellacassa E, Versini G, Henschke PA (2005) De novo synthesis of monoterpenes by Saccharomyces cerevisiae wine yeasts. FEMS Microbiol Lett 243:107–115

    Article  CAS  PubMed  Google Scholar 

  • Carroll AL, Desai SH, Atsumi S (2016) Microbial production of scent and flavor compounds. Curr Opin Biotechnol 37:8–15

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Cataldo VF, López J, Cárcamo M, Agosin E (2016) Chemical vs. biotechnological synthesis of C13-apocarotenoids: current methods, applications and perspectives. Appl Environ Microbiol 13:5703–5718

    Google Scholar 

  • D’Auria M, Mauriello G, Rana GL (2004) Volatile organic compounds from saffron. Flavour Fragr J 19:17–23

    Article  Google Scholar 

  • Dai Z, Nielsen J (2015) Advancing metabolic engineering through systems biology of industrial microorganisms. Curr Opin Biotechnol 36:8–15

    Article  PubMed  Google Scholar 

  • Debabov VG (2015) Modern approaches to the creation of industrial microorganism strains. Russ J Genet 51:365–376

    Article  CAS  Google Scholar 

  • Del Toro-Sánchez CL, Sánchez S, Ortiz MA, Villanueva S, Lugo-Cervantes E (2006) Generation of aroma compounds from Ditaxis heterantha by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 72:155–162

    Article  PubMed  Google Scholar 

  • Del Toro-Sánchez CL, Lugo-Cervantes E, Sánchez S (2015) Identification of bioproducts generated enzymatically by cell-free extracts of Saccharomyces cerevisiae from cells grown in the presence or absence of Heteranthin. Food Biotechnol 29:219–236

    Article  Google Scholar 

  • Du FL, Yu HL, Xu JH, Li CX (2014) Enhanced limonene production by optimizing the expression of limonene biosynthesis and MEP pathway genes in E. coli. Bioresour Bioprocess 1:10

    Article  Google Scholar 

  • Emmerstorfer-Augustin A, Moser S, Pichler H (2016) Screening for improved isoprenoid biosynthesis in microorganisms. J Biotechnol. doi:10.1016/j.jbiotec.2016.03.051

    PubMed  Google Scholar 

  • Frohwitter J, Heider SAE, Peters-Wendisch P, Beekwilder J, Wendisch VF (2014) Production of sesqiterpene (+)−valencene by metabolically engineered Corynebacterium glutamicum. J Biotechnol 191:205–213

    Google Scholar 

  • Fischer MJ, Meyer S, Claudel P, Bergdoll M, Karst F (2011) Metabolic engineering of monoterpene synthesis in yeast. Biotechnol Bioeng 108:1883–1892

    Article  CAS  PubMed  Google Scholar 

  • Harrison PJ, Bugg TDH (2014) Enzymology of the carotenoid cleavage dioxygenases: reaction mechanisms, inhibition and biochemical roles. Arch Biochem Biophys 544:105–111

    Article  CAS  PubMed  Google Scholar 

  • Halfmann C, Liping G, Gibbons W, Zhou R (2014) Genetically engineering cyanobacteria to convert CO2, water, and light into the long-chain hydrocarbon farnesene. Appl Microbiol Biotechnol 98:9869–9877

    Google Scholar 

  • Heider SAE, Peters-Wendisch P, Wendisch VF (2012) Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum. BMC Microbiol 12:1–11

    Article  Google Scholar 

  • Herrero Ó, Ramón D, Orejas M (2008) Engineering the Saccharomyces cerevisiae isoprenoid pathway for de novo production of aromatic monoterpenes in wine. Metab Eng 10:78–86

    Article  CAS  PubMed  Google Scholar 

  • Huang FC, Molnár P, Schwab W (2009) Cloning and functional characterization of carotenoid cleavage dioxygenase 4 genes. J Exp Bot 60:3011–3022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jongedijk E, Cankar K, Ranzijn J, van der Krol S, Bouwmeester H, Beekwilder J (2015) Capturing of the monoterpene olefin limonene produced in Saccharomyces cerevisiae. Yeast 32:159–171

    CAS  PubMed  Google Scholar 

  • Jongedijk E, Cankar K, Buchhaupt M, Schrader J, Bouwmeester H, Beekwilder J (2016) Biotechnological production of limonene in microorganisms. Appl Microbiol Biotechnol 100:2927–2938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kampranis SC, Makris AM (2012) Developing a yeast cell factory for the production of terpenoids. Comput Struct Biotechnol J 3:e201210006

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim SW, Kim JB, Jung WH, Kim JH, Jung JK (2006) Over-production of β-carotene from metabolically engineered Escherichia coli. Biotechnol Lett 28:897–904

    Article  CAS  PubMed  Google Scholar 

  • Krivoruchko A, Nielsen J (2015) Production of natural products through metabolic engineering of Saccharomyces cerevisiae. Curr Opin Biotechnol 35:7–15

    Article  CAS  PubMed  Google Scholar 

  • Lian J, Zhao H (2016) Functional reconstitution of a pyruvate dehydrogenase in the cytosol of Saccharomyces cerevisiae through lipoylation machinery engineering. ACS Synth Biol 5:689–697

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Zhang W, Du G, Chen J, Zhou J (2013) Overproduction of geraniol by enhanced precursor supply in Saccharomyces cerevisiae. J Biotechnol 168:446–451

    Google Scholar 

  • Liu W et al (2016) Engineering Escherichia coli for high-yield geraniol production with biotransformation of geranyl acetate to geraniol under fed-batch culture. Biotechnol Biofuels 9:58

    Article  PubMed  PubMed Central  Google Scholar 

  • Longo MA, Sanromán MA (2006) Production of food aroma compounds: microbial and enzymatic methodologies. Food Technol Biotechnol 44:335–353

    CAS  Google Scholar 

  • López J, Essus K, Kim IK, Pereira R, Herzog J, Siewers V, Nielsen J, Agosin E (2015) Production of β-ionone by combined expression of carotenogenic and plant CCD1 genes in Saccharomyces cerevisiae. Microb Cell Factories 14:1–13

    Article  Google Scholar 

  • Misawa N (2011) Pathway engineering for functional isoprenoids. Curr Opin Biotechnol 22:627–633

    Article  CAS  PubMed  Google Scholar 

  • Olson ML, Johnson J, Carswell WF, Reyes LH, Senger RS, Kao KC (2016) Characterization of an evolved carotenoids hyper-producer of Saccharomyces cerevisiae through bioreactor parameter optimization and Raman spectroscopy. J Ind Microbiol Biotechnol 43:1355–1363

    Article  CAS  PubMed  Google Scholar 

  • Pardo E, Rico J, Gil JV, Orejas M (2015) De novo production of six key grape aroma monoterpenes by a geraniol synthase-engineered S. cerevisiae wine strain. Microb Cell Factories 14:136

    Article  Google Scholar 

  • Raghavan S, Hansen J, Sonkar S, Kumar S, Kumar KK, Panchapagesa M, Hansen EH, Hansen KR (2014) Methods and materials for recombinant production of saffron compounds. WO2013021261 A3. Issued: 14.02.2013

    Google Scholar 

  • Reiling KK, Yoshikuni Y, Martin VJ, Newman J, Bohlmann J, Keasling JD (2004) Mono and diterpene production in Escherichia coli. Biotechnol Bioeng 87:200–212

    Article  CAS  PubMed  Google Scholar 

  • Renault H, Bassard JE, Hamberger B, Werck-Reichhart D (2014) Cytochrome P450-mediated metabolic engineering: current progress and future challenges. Curr Opin Plant Biol 19:27–34

    Article  CAS  PubMed  Google Scholar 

  • Reyes LH, Gomez JM, Kao KC (2014) Improving carotenoids production in yeast via adaptive laboratory evolution. Metab Eng 21:26–33

    Article  CAS  PubMed  Google Scholar 

  • Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MCY, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–943

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Bustamante E, Sánchez S (2007) Microbial production of C13-norisoprenoids and other aroma compounds via carotenoid cleavage. Crit Rev Microbiol 33:211–230

    Article  PubMed  Google Scholar 

  • Scalcinati G, Knuf C, Partow S, Chen Y, Maury J, Schalk M, Daviet L, Nielsen J, Siewers V (2012a) Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene α-santalene in a fed-batch mode. Metab Eng 14:91–103

    Article  CAS  PubMed  Google Scholar 

  • Scalcinati G, Partow S, Siewers V, Schalk M, Daviet L, Nielsen J (2012b) Combined metabolic engineering of precursor and co-factor supply to increase alpha-santalene production by Saccharomyces cerevisiae. Microb Cell Factories 11:117

    Article  CAS  Google Scholar 

  • Scholtmeijer K, Cankar K, Beekwilder J, Wösten HA, Lugones LG, Bosch D (2014) Production of (+)-valencene in the mushroom-forming fungus S. commune. Appl Microbiol Biotechnol 98:5059–5068

    Article  CAS  PubMed  Google Scholar 

  • Serra S (2015) Recent advances in the synthesis of carotenoid-derived flavours and fragrances. Molecules 20:12817–12840

    Article  CAS  PubMed  Google Scholar 

  • Toogood HS, Cheallaigh AN, Tait S, Mansell DJ, Jervis A, Lygidakis A, Humphreys L, Takano E, Gardiner JM, Scrutton NS (2015) Enzymatic menthol production: one-pot approach using engineered Escherichia coli. ACS Synth Biol 4:1112–1123

    Article  CAS  PubMed  Google Scholar 

  • van Rossum HM, Kozak BU, Pronk JT, van Marism AJA (2016) Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: pathway stoichiometry, free-energy conservation and redox-cofactor balancing. Metab Eng 36:99–115

    Article  PubMed  Google Scholar 

  • Verwaal R, Wang J, Meijnen JP, Visser H, Sandmann G, van den Berg JA, van Ooyen AJ (2007) High-level production of β-carotene in Saccharomyces cerevisiae by successive transformation with carotenogenic genes from Xanthophyllomyces dendrorhous. Appl Environ Microbiol 73:4342–4350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verwaal R, Jiang Y, Wang J, Daran JM, Sandmann G, van den Berg JA, van Ooyen AJ (2010) Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response. Yeast 27:983–998

    Article  CAS  PubMed  Google Scholar 

  • Vickers CE, Bongers M, Liu Q, Delatte T, Bouwmeester H (2014) Metabolic engineering of volatile isoprenoids in plants and microbes. Plant Cell Environ 37:1753–1775

    Article  CAS  PubMed  Google Scholar 

  • Vickers CE, Behrendorff JBYH, Bongers M, Brennan TCR, Bruschi M, Nielsen LK (2015) Production of industrially relevant isoprenoid compounds in engineered microbes. In: Kamm B, Idler C, Venus J (eds) Microorganisms in biorefineries. Springer, Berlin, pp 303–334

    Google Scholar 

  • Vik A, Rine J (2001) Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol 21:6395–6405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, Yoon SH, Jang HJ, Chung YR, Kim JY, Choi ES, Kim SW (2011) Metabolic engineering of Escherichia coli for α-farnesene production. Metab Eng 13:648–655

    Article  CAS  PubMed  Google Scholar 

  • Willrodt C, David C, Cornelissen S, BÃŒhler B, Julsing MK, Schmid A (2014) Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media. Biotechnol J 9:1000–1012

    Article  CAS  PubMed  Google Scholar 

  • Winkler JD, Kao KC (2014) Recent advances in the evolutionary engineering of industrial biocatalysts. Genomics 104:406–411

    Article  CAS  PubMed  Google Scholar 

  • Wriessnegger T, Pichler H (2013) Yeast metabolic engineering – targeting sterol metabolism and terpenoid formation. Prog Lipid Res 52:277–293

    Article  CAS  PubMed  Google Scholar 

  • Wriessnegger T, Augustin P, Engleder M, Leitner E, MÃŒller M, Kaluzna I, SchÃŒrmann M, Mink D, Zellnig G, Schwab H, Pichler H (2014) Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. Metab Eng 24:18–29

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y., Kuzuyama T, Komatsu M, Shin-Ya K, Omura S, Cane DE, Ikeda H (2015) Terpene synthases are widely distributed in bacteria. PNAS112:857–862

    Google Scholar 

  • Yang X, Nambou K, Wei L, Hua Q (2016) Heterologous production of α-farnesene in metabolically engineered strains of Yarrowia lipolytica. Bioresour Technol 216:1040–1048

    Article  CAS  PubMed  Google Scholar 

  • Zebec Z, Wilkes J, Jervis AJ, Scrutton NS, Takano E, Breitling R (2016) Towards synthesis of monoterpenes and derivatives using synthetic biology. Curr Opin Chem Biol 34:37–43

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Bao X, Li C, Shen Y, Hou J (2016) Improving monoterpene geraniol production through geranyl diphosphate synthesis regulation in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 100:4561–4571

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Wang C, Yoon SH, Jang HJ, Choi ES, Kim SW (2014) Engineering Escherichia coli for selective geraniol production with minimized endogenous dehydrogenation. J Biotechnol 169:42–50

    Article  CAS  PubMed  Google Scholar 

  • Zhu MM, Wang SL, Fan MT (2016) Isolation and identification of a novel β-carotene degrading microorganism from sea buckthorn juice. Food Biotechnol 30:1–17

    Article  Google Scholar 

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Authors and Affiliations

  1. Carlsberg Research Laboratory, J.C. Jacobsens Gade 4, 1799, Copenhagen V, Denmark

    Marta Mikš-Krajnik, Marta Zoglowek, Gemma Buron-Moles & Jochen Forster

  2. Faculty of Food Science, University of Warmia and Mazury in Olsztyn, PlacCieszyński 1, 10-726, Olsztyn, Poland

    Marta Mikš-Krajnik

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  1. Marta Mikš-Krajnik
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  2. Marta Zoglowek
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  3. Gemma Buron-Moles
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  4. Jochen Forster
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Correspondence to Jochen Forster .

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  1. Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea (Republic of)

    Sang Yup Lee

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Mikš-Krajnik, M., Zoglowek, M., Buron-Moles, G., Forster, J. (2017). Microbial Production of Flavors and Fragrances. 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_375

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