Characterization of biosynthetic genes of ascamycin/dealanylascamycin featuring a 5'-O-sulfonamide moiety in Streptomyces sp. JCM9888

PLoS One. 2014 Dec 5;9(12):e114722. doi: 10.1371/journal.pone.0114722. eCollection 2014.

Abstract

Ascamycin (ACM) and dealanylascamycin (DACM) are nucleoside antibiotics elaborated by Streptomyces sp. JCM9888. The later shows broad spectrum inhibition activity to various gram-positive and gram-negative bacteria, eukaryotic Trypanosoma and is also toxic to mice, while ascamycin is active against very limited microorganisms, such as Xanthomonas. Both compounds share an unusual 5'-O-sulfonamide moiety which is attached to an adenosine nucleoside. In this paper, we first report on the 30 kb gene cluster (23 genes, acmA to acmW) involved in the biosynthesis of these two antibiotics and a biosynthetic assembly line was proposed. Of them, six genes (AcmABGKIW) are hypothetical genes involved in 5'-O-sulfonamide formation. Two flavin adenine dinucleotide (FAD)-dependent chlorinase genes acmX and acmY were characterized which are significantly remote from acmA-W and postulated to be required for adenine C2-halogenation. Notably gene disruption of acmE resulted in a mutant which could only produce dealanylascamycin but was blocked in its ability to biosynthesize ascamycin, revealing its key role of conversion of dealanylascamycin to ascamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Chloroadenosine / analogs & derivatives*
  • 2-Chloroadenosine / chemistry
  • 2-Chloroadenosine / metabolism
  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / genetics
  • Adenosine / metabolism
  • Genes, Bacterial*
  • Molecular Sequence Data
  • Multigene Family
  • Streptomyces / genetics*
  • Streptomyces / metabolism*
  • Sulfonamides / chemistry
  • Sulfonamides / metabolism

Substances

  • Sulfonamides
  • 2-Chloroadenosine
  • 5'-sulfamoyl-2-chloroadenosine
  • ascamycin
  • Adenosine

Associated data

  • GENBANK/KJ817374
  • GENBANK/KJ817375

Grants and funding

The authors gratefully acknowledge grants from the 973 Program (2009CB118901, 2012CB721002), Ministry of Science and Technology, China, and the National Natural Science Foundation of China. CZ is a recipient of China postdoctoral training project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.