Exploitation of the unique reaction in microbial meroterpenoid biosynthesis

Title Exploitation of the unique reaction in microbial meroterpenoid biosynthesis
Lecturer Dr. Takayoshi Awakawa (Assistant Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo)
Language English
Date&Time 04/24/2017 (Mon) 15:00~16:00
Venue Seminar Room L12
Detail Many different kinds of secondary metabolites have been isolated from microorganism so far. To study their biosynthetic reactions is important, because the secondary metabolites exhibit various bioactivities against the others and the biosynthetic study leads to the exploitation of useful bioactive compounds including pharmaceutical agents. In this presentation, two main topics of the biosynthetic study on the microbial meroterpenoids, a group of hybrid compounds consisting of terpenoid and other biosynthetic origin, will be discussed. In both cases, the heterologous gene expression system in microorganisms played a key role to elucidate the biosynthetic pathway. First, the biosynthesis of fungal meroterpenoids, consisting of polyketide and terpenoid, will be presented. The gene expression system in Aspergillus oryzae enabled us to explore the catalyses of unique terpene cyclase and oxidase.1-2) With this powerful gene expression system, now we can efficiently explore the new biosynthetic genes found with bioinformatic analysis of genome database. Secondly, the biosynthesis of actinomycete meroterpenoid with indole and terpenoid, will be presented. The screening method based on the multiple gene expression system successfully identified one key biosynthetic genes located outside of the gene cluster.3) In vitro assay with synthetic substrate revealed unprecedented terpene cyclization reaction triggered by methylation. With complexed with the structural studies of enzyme, these studies paved the way to create unnatural bioactive meroteroenoids.4) 1) Matsuda, Y.; Awakawa, T.; Itoh, T.; Wakimoto, T.; Kushiro, T.; Fujii, I.; Ebizuka, Y.; Abe, I. ChemBioChem 2012, 13, 1738. 2) Matsuda, Y.; Awakawa, T.; Wakimoto, T.; Abe, I. J. Am. Chem. Soc. 2013, 135, 10962. 3) Awakawa, T.; Zhang, L.; Wakimoto, T.; Hoshino, S.; Mori, T.; Ito, T.; Ishikawa, J.; Tanner, M. E.; Abe, I. J. Am. Chem. Soc. 2014, 136, 9910. 4) Mori, T.; Zhang, L.; Awakawa, T.; Hoshino, S.; Okada, M.; Morita, H.; Abe, I. Nat. Commun. 2016, 7, 10849.
Contact ストレス微生物科学
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