Mining novel biosynthetic machineries of secondary metabolites from actinobacteria

ABSTRACT

Secondary metabolites produced by actinobacteria have diverse structures and important biological activities, making them a useful source of drug development. Diversity of the secondary metabolites indicates that the actinobacteria exploit various chemical reactions to construct a structural diversity. Thus, studying the biosynthetic machinery of these metabolites should result in discovery of various enzymes catalyzing interesting and useful reactions. This review summarizes our recent studies on the biosynthesis of secondary metabolites from actinobacteria, including the biosynthesis of nonproteinogenic amino acids used as building blocks of nonribosomal peptides, the type II polyketide synthase catalyzing polyene scaffold, the nitrous acid biosynthetic pathway involved in secondary metabolite biosynthesis and unique cytochrome P450 catalyzing nitrene transfer. These findings expand the knowledge of secondary metabolite biosynthesis machinery and provide useful tools for future bioengineering.

Graphical abstract

Biosynthesis of secondary metabolites produced by actinobacteria exploits various chemical reactions to construct a structural diversity.

KEYWORDS:

• Biosynthesis
• actinobacteria
• polyketide
• nonribosomal peptide
• secondary metabolite

Acknowledgments

These studies were carried out at The University of Tokyo, and Saarladn University. I am very grateful to Professors Sueharu Horinouchi, Yasuo Ohnishi, and Rolf Müller for their support and helpful discussions. I thank all my co-workers for their cooperation. I also would like to thank all the members of the Laboratory of Fermentation who participated in this work. This research was supported by Japan Society for the Promotion of Science [grant number 25850048, 25108706, 17H05432 and 18H02144], the NC-CARP project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), CREST, JST, JSPS A3 Foresight Program and Amano Enzyme Inc.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This research was supported by Japan Society for the Promotion of Science [grant number 25850048, 25108706, 17H05432 and 18H02144], the NC-CARP project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), CREST, Japan Science andTechnology Agency (JST, JPMJCR13B3), JSPS A3 Foresight Program Enzyme Inc.