Discovery of Streptomyces secondary metabolite pathway mediated by amino-group carrier proteins

September 26, 2016

Researchers in The University of Tokyo previously discovered amino-group carrier proteins (AmCPs) in thermophilic bacteria and archaea involved in lysine and arginine biosynthesis. While searching among various organisms for the presence of the amcp gene, the researchers found a positive match for Streptomyces, a widely studied bacteria known as a repository of diverse bioactive substances.

For this joint research, researchers from RIKEN CSRS and Juntendo University joined The University of Tokyo researchers to analyze AmCP functions in Streptomyces, from which they determined that the protein mediates synthesis of the previously uncharacterized nonproteinogenic amino acid DADH.

They also found that genes in the vicinity of amcp coded for enzymes that convert DADH to a novel peptide, vazabitide A, with a distinctive azabicyclo-ring structure. From this, the researchers were able to demonstrate that AmCP contributes to secondary metabolism, not just primary metabolism. DADH also showed biological activity to inhibit hypocotyl elongation of Arabidodpsis.

As scientists continue to uncover that amcp-like genes are widely distributed across the Streptomyces genome, we can expect the discovery of various novel AmCP-mediated natural compounds and the application to develop novel hervicide based on DADH.

 

Original article
Nature Chemical Biology doi:10.1038/nchembio.2181
F. Hasebe, K. Matsuda, T. Shiraishi, Y. Futamura, T. Nakano, T. Tomita, K. Ishigami, H. Taka, R. Mineki, T. Fujimura, H. Osada, T. Kuzuyama, M. Nishiyama,
"Amino group carrier protein-mediated secondary metabolite biosynthesis in Streptomyces".

Contact
Hiroyuki Osada; Group Director, Chemical Biology Research Group
Takeshi Nakano; Senior Research Scientist, Gene Discovery Research Group