Identification of two novel anti-fibrotic benzopyran compounds produced by engineered strains derived from Streptomyces xiamenensis M1-94P that originated from deep-sea sediments

Mar Drugs. 2013 Oct 22;11(10):4035-49. doi: 10.3390/md11104035.


The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology
  • Fibroblasts / drug effects
  • Fibrosis / drug therapy
  • Geologic Sediments / chemistry*
  • Geologic Sediments / microbiology*
  • Humans
  • Lung / drug effects
  • Mutation / genetics
  • Ribosomes / genetics
  • Streptomyces / chemistry*
  • Streptomyces / genetics*
  • Threonine / analogs & derivatives
  • Threonine / chemistry
  • Threonine / pharmacology


  • Benzopyrans
  • N-((3,4-dihydro-3-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-2H-1-benzopyran-6-yl)carbonyl)threonine
  • Threonine