Expansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products

Yuta Kudo, Takayoshi Awakawa, Yi Ling Du, Peter A. Jordan, Kaitlin E. Creamer, Paul R. Jensen, Roger G. Linington, Katherine S. Ryan, Bradley S. Moore

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)3253-3261
Number of pages9
JournalACS Chemical Biology
Volume15
Issue number12
DOIs
Publication statusPublished - 2020 Dec 18

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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