Small molecules that enhance the production of natural products

September 11, 2020

β-carboline mechanism of action that enhances secondary metabolite production

RIKEN CSRS has found the mechanism by which the production of "reveromycin A (RM-A)," a secondary metabolite of Actinomycetes bacteria, is enhanced via the LuxR family transcriptional regulator when "β-carboline derivative" is added.

Actinomycetes bacteria are known as a “repository” of useful bioactive compounds that can be used in pharmaceuticals and agricultural chemicals. Although more than 30 secondary metabolite biosynthetic gene clusters have been found in previous genomic analysis, many of them are dormant gene clusters. Understanding bioactivation mechanism of secondary metabolite biosynthetic gene clusters is important for development of novel natural products that can be a drug seed. A joint research group has previously reported that addition of β-carboline derivatives (BR-1) during the growth of Streptomyces sp. SN-593 enhances RM-A production. This study showed that binding of BR-1 to the LuxR family transcriptional regulator (RevU) accelerates the binding to its promoter region in upstream of the revU gene and enhances the expression of the entire RM-A biosynthetic gene cluster. In addition, the group found that BR-1 also enhances the production of secondary metabolites in different types of Actinomycetes bacteria.

The results of this study are expected to lead to development of novel natural products using gene clusters controlled by similar transcriptional regulators.

Original article
Scientific Reports doi:10.1038/s41598-020-66974-y
S. Panthee, N. Kito, T. Hayashi, T. Shimizu, J. Ishikawa, H. Hamamoto, H. Osada & S. Takahashi,
"β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593".
Shunji Takahashi
Unit Leader
Natural Product Biosynthesis Research Unit