Biosynthesis of spectinomycin: heterologous production of spectinomycin and spectinamine in an aminoglycoside-deficient host, Streptomyces venezuelae YJ003

J Appl Microbiol. 2008 Jul;105(1):300-8. doi: 10.1111/j.1365-2672.2008.03788.x. Epub 2008 Mar 18.

Abstract

Aims: To obtain spectinomycin and spectinamine by heterologous expression into the biosynthetic deoxysugar (desosamine) gene-deleted host Streptomyces venezuelae YJ003.

Methods and results: The 17-kb spectinomycin biosynthetic gene cluster from Streptomyces spectabilis ATCC 27741 was heterologously expressed into Streptomyces venezuelae YJ003. Furthermore, the speA, speB and spcS2 encoded in the spectinomycin biosynthetic gene cluster of cosmid pSPC8 were also heterologously characterized to be responsible for the production of spectinamine.

Conclusions: The results of this study indicated that pSPC8 contains all the genes necessary for the biosynthesis of spectinomycin. We also concluded that SpeA, SpeB and SpcS2 are sufficient for the biosynthesis of spectinamine. We also verified that SpeB and SpcS2 show dual character in the biosynthetic pathway of spectinomycin in Streptomyces spectabilis.

Significance and impact of the study: This is the report regarding the expression of a biosynthetic gene cluster that gives rise to the production of aminoglycoside antibiotics in Streptomyces venezuelae YJ003. Therefore, this work may serve as a foundation for further research on spectinomycin biosynthesis and other aminoglycosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / biosynthesis*
  • Aminoglycosides / genetics
  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / drug effects
  • Bioreactors / microbiology*
  • Genetic Engineering
  • Microbial Sensitivity Tests
  • Multigene Family*
  • Spectinomycin / biosynthesis*
  • Spectinomycin / chemistry
  • Spectinomycin / pharmacology
  • Streptomyces / genetics
  • Streptomyces / metabolism*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Spectinomycin