Discovery of a Tambjamine Gene Cluster in Streptomyces Suggests Convergent Evolution in Bipyrrole Natural Product Biosynthesis

ACS Chem Biol. 2023 Feb 17;18(2):223-229. doi: 10.1021/acschembio.2c00685. Epub 2023 Jan 4.

Abstract

While bacterial natural products are a valuable source of therapeutics, the molecules produced by most biosynthetic gene clusters remain unknown. Tambjamine YP1, produced by Pseudoalteromonas tunicata, is partially derived from fatty acids siphoned from primary metabolism. A structurally similar tambjamine produced by Streptomyces, BE-18591, had not been linked to a gene cluster. Using enzymes putatively implicated in the construction of these two tambjamines, we used sequence similarity networks and gene knockout experiments to identify the biosynthetic gene cluster responsible for the production of tambjamine BE-18591 in Streptomyces albus. Despite the structural similarities between YP1 and BE-18591, the biosynthesis of the alkylamine tails of these molecules differs significantly, with the S. albus gene cluster putatively encoding a dedicated system for the construction of the fatty acid precursor to BE-18591. These different pathways in Pseudoalteromonas and Streptomyces suggest that evolutionary convergence is operative, with similar selective pressures leading to the emergence of structurally similar tambjamine natural products using different biosynthetic logic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products* / metabolism
  • Multigene Family
  • Streptomyces* / genetics
  • Streptomyces* / metabolism

Substances

  • Biological Products