Disruption of a methyltransferase gene in actinomycin G gene cluster in Streptomyces iakyrus increases the production of phenazinomycin

Zhiwei Qin, Xiaoling Wang, Mostafa Rateb, Lina Adnan Ass'ad, Marcel Jaspars, Zixin Deng, Yi Yu (Corresponding Author), Hai Deng (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Phenazinomycin is a hybrid natural product consisting of two chemical entities, a phenazine and a cyclic terpenoid. Phenazinomycin exhibits potent activity against murine tumors and adriamycin-resistant P388 leukemia cells. Streptomyces iakyrus DSM 41873 is known to produce five actinomycin G2 -G6 . In the previous study, we identified the gene cluster directing the biosynthesis of actinomycin G2 -G4 . Inactivation of acmG5' gene in the actinomycin G gene cluster in S. iakyrus completely abolished the production of actinomycin G. Metabolic profiling, chemical isolation, and structural elucidation of the resulting mutant SIAΔacmG5' showed a previously unnoticed metabolite phenazinomycin in S. iakyrus. In silico analysis identified a hybrid biosynthetic gene cluster in the genome of S. iakyrus that could be responsible for the biosynthesis of phenazinomycin. It is proposed that the perturbation of actinomycin G to enhance the phenazinomycin production in the mutant may result from the lifted competition of chorismate, the common precursor of the biosynthetic pathways of these two structurally unrelated natural products.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalFEMS Microbiology Letters
Volume352
Issue number1
Early online date27 Jan 2014
DOIs
Publication statusPublished - Mar 2014

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Keywords

  • phenazinomycin
  • biosynthesis
  • gene disruption
  • structural elucidation

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