Advertisement

Microbial Production of Flavors and Fragrances

  • Marta Mikš-Krajnik
  • Marta Zoglowek
  • Gemma Buron-Moles
  • Jochen Forster
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (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.

References

  1. 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 77:1033–1040Google Scholar
  2. 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 19:33–41CrossRefPubMedGoogle Scholar
  3. 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 28:123–133CrossRefPubMedGoogle Scholar
  4. Amiri P, Shahpiri A, Asadollahi MA, Momenbeik F, Partow S (2016) Metabolic engineering of Saccharomyces cerevisiae for linalool production. Biotechnol Lett 38:503–508CrossRefPubMedGoogle Scholar
  5. Asadollahi MA, Maury J, Møller 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 99:666–677CrossRefPubMedGoogle Scholar
  6. 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 89:401–411CrossRefPubMedGoogle Scholar
  7. 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:383–392CrossRefGoogle Scholar
  8. 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 319–327Google Scholar
  9. 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 109:2513–2522CrossRefPubMedGoogle Scholar
  10. 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 81:3316–3325CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brochado AR, Matos C, Møller BL, Hansen J, Mortensen UH, Patil KR (2010) Improved vanillin production in baker’s yeast through in silico design. Microb Cell Factories 9:84CrossRefGoogle Scholar
  12. 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 243:107–115CrossRefPubMedGoogle Scholar
  13. Carroll AL, Desai SH, Atsumi S (2016) Microbial production of scent and flavor compounds. Curr Opin Biotechnol 37:8–15CrossRefPubMedGoogle Scholar
  14. Carter OA, Peters RJ, Croteau R (2003) Monoterpene biosynthesis pathway construction in Escherichia coli. Phytochemistry 64:425–433CrossRefPubMedGoogle Scholar
  15. Cataldo VF, López J, Cárcamo M, Agosin E (2016) Chemical vs. biotechnological synthesis of C13-apocarotenoids: current methods, applications and perspectives. Appl Environ Microbiol 13:5703–5718Google Scholar
  16. D’Auria M, Mauriello G, Rana GL (2004) Volatile organic compounds from saffron. Flavour Fragr J 19:17–23CrossRefGoogle Scholar
  17. Dai Z, Nielsen J (2015) Advancing metabolic engineering through systems biology of industrial microorganisms. Curr Opin Biotechnol 36:8–15CrossRefPubMedGoogle Scholar
  18. Debabov VG (2015) Modern approaches to the creation of industrial microorganism strains. Russ J Genet 51:365–376CrossRefGoogle Scholar
  19. 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 72:155–162CrossRefPubMedGoogle Scholar
  20. 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 29:219–236CrossRefGoogle Scholar
  21. 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 1:10CrossRefGoogle Scholar
  22. Emmerstorfer-Augustin A, Moser S, Pichler H (2016) Screening for improved isoprenoid biosynthesis in microorganisms. J Biotechnol. doi:10.1016/j.jbiotec.2016.03.051PubMedGoogle Scholar
  23. Frohwitter J, Heider SAE, Peters-Wendisch P, Beekwilder J, Wendisch VF (2014) Production of sesqiterpene (+)−valencene by metabolically engineered Corynebacterium glutamicum. J Biotechnol 191:205–213Google Scholar
  24. Fischer MJ, Meyer S, Claudel P, Bergdoll M, Karst F (2011) Metabolic engineering of monoterpene synthesis in yeast. Biotechnol Bioeng 108:1883–1892CrossRefPubMedGoogle Scholar
  25. Harrison PJ, Bugg TDH (2014) Enzymology of the carotenoid cleavage dioxygenases: reaction mechanisms, inhibition and biochemical roles. Arch Biochem Biophys 544:105–111CrossRefPubMedGoogle Scholar
  26. 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 98:9869–9877Google Scholar
  27. Heider SAE, Peters-Wendisch P, Wendisch VF (2012) Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum. BMC Microbiol 12:1–11CrossRefGoogle Scholar
  28. Herrero Ó, Ramón D, Orejas M (2008) Engineering the Saccharomyces cerevisiae isoprenoid pathway for de novo production of aromatic monoterpenes in wine. Metab Eng 10:78–86CrossRefPubMedGoogle Scholar
  29. Huang FC, Molnár P, Schwab W (2009) Cloning and functional characterization of carotenoid cleavage dioxygenase 4 genes. J Exp Bot 60:3011–3022CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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 32:159–171PubMedGoogle Scholar
  31. Jongedijk E, Cankar K, Buchhaupt M, Schrader J, Bouwmeester H, Beekwilder J (2016) Biotechnological production of limonene in microorganisms. Appl Microbiol Biotechnol 100:2927–2938CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kampranis SC, Makris AM (2012) Developing a yeast cell factory for the production of terpenoids. Comput Struct Biotechnol J 3:e201210006CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kim SW, Kim JB, Jung WH, Kim JH, Jung JK (2006) Over-production of β-carotene from metabolically engineered Escherichia coli. Biotechnol Lett 28:897–904CrossRefPubMedGoogle Scholar
  34. Krivoruchko A, Nielsen J (2015) Production of natural products through metabolic engineering of Saccharomyces cerevisiae. Curr Opin Biotechnol 35:7–15CrossRefPubMedGoogle Scholar
  35. Lian J, Zhao H (2016) Functional reconstitution of a pyruvate dehydrogenase in the cytosol of Saccharomyces cerevisiae through lipoylation machinery engineering. ACS Synth Biol 5:689–697CrossRefPubMedGoogle Scholar
  36. Liu J, Zhang W, Du G, Chen J, Zhou J (2013) Overproduction of geraniol by enhanced precursor supply in Saccharomyces cerevisiae. J Biotechnol 168:446–451Google Scholar
  37. 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 9:58CrossRefPubMedPubMedCentralGoogle Scholar
  38. Longo MA, Sanromán MA (2006) Production of food aroma compounds: microbial and enzymatic methodologies. Food Technol Biotechnol 44:335–353Google Scholar
  39. 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 14:1–13CrossRefGoogle Scholar
  40. Misawa N (2011) Pathway engineering for functional isoprenoids. Curr Opin Biotechnol 22:627–633CrossRefPubMedGoogle Scholar
  41. 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 43:1355–1363CrossRefPubMedGoogle Scholar
  42. 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 14:136CrossRefGoogle Scholar
  43. 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: 14.02.2013Google Scholar
  44. Reiling KK, Yoshikuni Y, Martin VJ, Newman J, Bohlmann J, Keasling JD (2004) Mono and diterpene production in Escherichia coli. Biotechnol Bioeng 87:200–212CrossRefPubMedGoogle Scholar
  45. Renault H, Bassard JE, Hamberger B, Werck-Reichhart D (2014) Cytochrome P450-mediated metabolic engineering: current progress and future challenges. Curr Opin Plant Biol 19:27–34CrossRefPubMedGoogle Scholar
  46. Reyes LH, Gomez JM, Kao KC (2014) Improving carotenoids production in yeast via adaptive laboratory evolution. Metab Eng 21:26–33CrossRefPubMedGoogle Scholar
  47. 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 440:940–943CrossRefPubMedGoogle Scholar
  48. Rodríguez-Bustamante E, Sánchez S (2007) Microbial production of C13-norisoprenoids and other aroma compounds via carotenoid cleavage. Crit Rev Microbiol 33:211–230CrossRefPubMedGoogle Scholar
  49. 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 14:91–103CrossRefPubMedGoogle Scholar
  50. 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 11:117CrossRefGoogle Scholar
  51. 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 98:5059–5068CrossRefPubMedGoogle Scholar
  52. Serra S (2015) Recent advances in the synthesis of carotenoid-derived flavours and fragrances. Molecules 20:12817–12840CrossRefPubMedGoogle Scholar
  53. 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 4:1112–1123CrossRefPubMedGoogle Scholar
  54. 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 36:99–115CrossRefPubMedGoogle Scholar
  55. 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 73:4342–4350CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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 27:983–998CrossRefPubMedGoogle Scholar
  57. Vickers CE, Bongers M, Liu Q, Delatte T, Bouwmeester H (2014) Metabolic engineering of volatile isoprenoids in plants and microbes. Plant Cell Environ 37:1753–1775CrossRefPubMedGoogle Scholar
  58. 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 303–334Google Scholar
  59. Vik A, Rine J (2001) Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol 21:6395–6405CrossRefPubMedPubMedCentralGoogle Scholar
  60. 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 13:648–655CrossRefPubMedGoogle Scholar
  61. Willrodt C, David C, Cornelissen S, Bühler B, Julsing MK, Schmid A (2014) Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media. Biotechnol J 9:1000–1012CrossRefPubMedGoogle Scholar
  62. Winkler JD, Kao KC (2014) Recent advances in the evolutionary engineering of industrial biocatalysts. Genomics 104:406–411CrossRefPubMedGoogle Scholar
  63. Wriessnegger T, Pichler H (2013) Yeast metabolic engineering – targeting sterol metabolism and terpenoid formation. Prog Lipid Res 52:277–293CrossRefPubMedGoogle Scholar
  64. Wriessnegger T, Augustin P, Engleder M, Leitner E, Müller M, Kaluzna I, Schürmann M, Mink D, Zellnig G, Schwab H, Pichler H (2014) Production of the sesquiterpenoid (+)-nootkatone by metabolic engineering of Pichia pastoris. Metab Eng 24:18–29CrossRefPubMedGoogle Scholar
  65. Yamada Y., Kuzuyama T, Komatsu M, Shin-Ya K, Omura S, Cane DE, Ikeda H (2015) Terpene synthases are widely distributed in bacteria. PNAS112:857–862Google Scholar
  66. Yang X, Nambou K, Wei L, Hua Q (2016) Heterologous production of α-farnesene in metabolically engineered strains of Yarrowia lipolytica. Bioresour Technol 216:1040–1048CrossRefPubMedGoogle Scholar
  67. 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 34:37–43CrossRefPubMedGoogle Scholar
  68. 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 100:4561–4571CrossRefPubMedGoogle Scholar
  69. 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 169:42–50CrossRefPubMedGoogle Scholar
  70. Zhu MM, Wang SL, Fan MT (2016) Isolation and identification of a novel β-carotene degrading microorganism from sea buckthorn juice. Food Biotechnol 30:1–17CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Marta Mikš-Krajnik
    • 1
    • 2
  • Marta Zoglowek
    • 1
  • Gemma Buron-Moles
    • 1
  • Jochen Forster
    • 1
  1. 1.Carlsberg Research LaboratoryCopenhagen VDenmark
  2. 2.Faculty of Food ScienceUniversity of Warmia and Mazury in OlsztynOlsztynPoland

Personalised recommendations