1. Expansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products
- Author
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Bradley S. Moore, Kaitlin E. Creamer, Yi-Ling Du, Roger G. Linington, Katherine S. Ryan, Takayoshi Awakawa, Paul R. Jensen, Yuta Kudo, and Peter A. Jordan
- Subjects
Biological Products ,Cell signaling ,biology ,Operon ,Chemistry ,Esters ,General Medicine ,Bridged Bicyclo Compounds, Heterocyclic ,biology.organism_classification ,Biochemistry ,Streptomyces ,Article ,In vitro ,chemistry.chemical_compound ,4-Butyrolactone ,Biosynthesis ,Genes, Bacterial ,Gene cluster ,Molecular Medicine ,Gene ,Bacteria ,Signal Transduction - 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.
- Published
- 2020