From gene resources to compound resources

December 15, 2020

Stable production with the heterologous expression of biosynthetic genes

RIKEN CSRS has successfully expressed all of the biosynthetic genes for verticilactam, a secondary metabolite of actinomycetes, Streptomyces spiroverticillatus JC-8444, and produced verticilactam and its new analogues.

While many secondary metabolites produced by actinomycetes have been developed as pharmaceuticals and pesticides, the production decreases with the passages of producing strain in some cases. Therefore, the techniques to produce the secondary metabolites in optimized heterologous host are important for the stable supply of useful compounds.

A joint research group identified a biosynthetic gene cluster for verticilactam and introduced it into the heterologous host Streptomyces avermitilis SUKA17 strain to create a transformed strain and produce verticilactam. Confirming production of new analogues of verticilactam, the group isolated them and determined the structure. In addition, they determined the absolute configuration of verticilactam, which had been unknown, using computational chemistry methods. The group also showed that verticilactam has antimalarial activity.

The results of this study are expected to contribute to stable production of microbial secondary metabolites , and to creation of new natural compounds.

Original article
Journal of Natural Products doi:10.1021/acs.jnatprod.0c00755
T. Nogawa, A. Terai, K. Amagai, J. Hashimoto, Y. Futamura, A. Okano, M. Fujie, N. Satoh, H. Ikeda, K. Shin-ya, H. Osada, S. Takahashi,
"Heterologous expression of the biosynthetic gene cluster for Verticilactam and identification of analogues".
Shunji Takahashi; Unit Leader
Natural Product Biosynthesis Research Unit
Hiroyuki Osada; Group Director
Toshihiko Nogawa; Research Scientist
Chemical Biology Research Group