Formation of Isoprenoids
Isoprenoids, also known as terpenoids, are a diverse group of metabolites produced in all free-living organisms. They play an indispensable role in a wide variety of essential processes but also contribute to a better adaptation to the environment in the form of specialized secondary metabolites. In spite of their notable structural and functional diversity, all isoprenoids are synthesized from the same metabolic precursors, which are then converted into prenyl diphosphates of increasing length. Such basic prenyl diphosphate intermediates represent the starting point of downstream pathways leading to the formation of the vast diversity of end products. Here we present an overview of isoprenoid biosynthesis in microbes from the three kingdoms of life, namely, bacteria, archaea, and eukaryotic microorganisms (mainly microalgae and yeast), with a special emphasis on the research conducted during the last decade. We also discuss the main functional classes of isoprenoids occurring in these microorganisms by focusing in the representative model organisms of each kingdom. Finally, we examine key research needs in this field. This includes expanding our understanding of secondary isoprenoid metabolism in microbes, examining the evolutionary relationships between the two core biosynthetic pathways and improving our ability to engineer production of industrially useful isoprenoids in microbes.
Research at the authors’ laboratories was supported by a Marie Curie International outgoing Fellowship within the 7th European Community Framework Programme to JPG, an ERA-IB-2 project funded by the Spanish MINECO (PCIN-2015-103) to MRC, and a Queensland Government Accelerate Fellowship to CEV.
- Begley M, Bron PA, Heuston S, Casey PG, Englert N, Wiesner J, Jomaa H, Gahan CG, Hill C (2008) Analysis of the isoprenoid biosynthesis pathways in Listeria monocytogenes reveals a role for the alternative 2-C-methyl-D-erythritol 4-phosphate pathway in murine infection. Infect Immun 76:5392–5401CrossRefPubMedPubMedCentralGoogle Scholar
- Carretero-Paulet L, Lipska A, Perez-Gil J, Sangari FJ, Albert VA, Rodriguez-Concepcion M (2013) Evolutionary diversification and characterization of the eubacterial gene family encoding DXR type II, an alternative isoprenoid biosynthetic enzyme. BMC Evol Biol 13:180CrossRefPubMedPubMedCentralGoogle Scholar
- Frank HA (1999) Incorporation of carotenoids into reaction Center and light-harvesting pigment-protein complexes. In: Frank HA, Young AJ, Britton G, Cogdell RJ (eds) The photochemistry of carotenoids. Springer, Dordrecht, pp 235–244Google Scholar
- Frank A, Groll M (2017) The methylerythritol phosphate pathway to isoprenoids. Chem Rev 117:5675–5703Google Scholar
- Meadows AL, Hawkins KM, Tsegaye Y, Antipov E, Kim Y, Raetz L, Dahl RH, Tai A, Mahatdejkul-Meadows T, Xu L, Zhao L, Dasika MS, Murarka A, Lenihan J, Eng D, Leng JS, Liu CL, Wenger JW, Jiang H, Chao L, Westfall P, Lai J, Ganesan S, Jackson P, Mans R, Platt D, Reeves CD, Saija PR, Wichmann G, Holmes VF, Benjamin K, Hill PW, Gardner TS, Tsong AE (2016) Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature 537:694–697CrossRefPubMedGoogle Scholar
- Nitschke W, Kramer D, Riedel A, Liebl U (1995) From naphtho-to benzoquinones-(r) evolutionary reorganizations of electron transfer chains. Photosynthesis: From Light to Biosphere 1:945–950Google Scholar
- Perez-Gil J, Uros EM, Sauret-Gueto S, Lois LM, Kirby J, Nishimoto M, Baidoo EE, Keasling JD, Boronat A, Rodriguez-Concepcion M (2012b) Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway. PLoS One 7:e43775CrossRefPubMedPubMedCentralGoogle Scholar
- Sangari FJ, Perez-Gil J, Carretero-Paulet L, Garcia-Lobo JM, Rodriguez-Concepcion M (2010) A new family of enzymes catalyzing the first committed step of the methylerythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in bacteria. Proc Natl Acad Sci U S A 107:14081–14086CrossRefPubMedPubMedCentralGoogle Scholar
- Touz ET, Mengin-Lecreulx D (2008) Undecaprenyl phosphate synthesis. EcoSal Plus 2013; doi: 10.1128/ecosalplus.220.127.116.11
- Vannice JC, Skaff DA, Keightley A, Addo JK, Wyckoff GJ, Miziorko HM (2014) Identification in Haloferax volcanii of phosphomevalonate decarboxylase and isopentenyl phosphate kinase as catalysts of the terminal enzyme reactions in an archaeal alternate mevalonate pathway. J Bacteriol 196:1055–1063CrossRefPubMedPubMedCentralGoogle 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 (ed) Microorganisms in biorefineries. Springer, Berlin/Heidelberg, pp 303–334Google Scholar
- Warlick BP, Evans BS, Erb TJ, Ramagopal UA, Sriram J, Imker HJ, Sauder JM, Bonanno JB, Burley SK, Tabita FR, Almo SC, Sweedler JS, Gerlt JA (2012) 1-methylthio-D-xylulose 5-phosphate methylsulfurylase: a novel route to 1-deoxy-D-xylulose 5-phosphate in Rhodospirillum rubrum. Biochemistry 51:8324–8326CrossRefPubMedPubMedCentralGoogle Scholar