Open AccessExpansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products
Author(s) -
Yuta Kudo,
Takayoshi Awakawa,
YiLing Du,
Peter Jordan,
Kaitlin E. Creamer,
Paul R. Jensen,
Roger G. Linington,
Katherine S. Ryan,
Bradley S. Moore
Publication year - 2020
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.0c00824
Subject(s) - operon , gene cluster , streptomyces , gene , biology , biosynthesis , bacteria , biochemistry , structural motif , genetics , escherichia coli
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 antimalarial 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 salinipostins and newly identified natural A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed among many actinomycete genera, including Streptomyces , suggesting the significance of this operon in bacteria.