Expansion of gamma-butyrolactone signaling molecule biosynthesis to phosphotriester natural products

Published: Oct. 11, 2020, 8:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.11.335315v1?rss=1 Authors: Kudo, Y., Awakawa, T., Du, Y.-L., Jordan, P. A., Creamer, K. E., Jensen, P. R., Linington, R. G., Ryan, K. S., Moore, B. S. Abstract: Bacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in Streptomyces species and display species-specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus Salinispora based on their anti-malarial properties. As the salinipostins possess a rare phosphotriester motif of unknown biosynthetic origin, we set out to explore its construction by the widely conserved 9-gene spt operon in Salinispora species. We show through a series of in vivo and in vitro studies that the spt gene cluster dually encodes the saliniphostins and newly identified A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed amongst many actinomycete genera, including Streptomyces, suggesting the significance of this operon in bacteria. Copy rights belong to original authors. Visit the link for more info