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

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.

• Authors: Zhiwei Qin, Xiaoling Wang, Mostafa Ezzat Rateb, Lina Adnan Ass'ad, Marcel Jaspars, Zixin Deng, Yi Yu, Hai Deng
• Journal: FEMS microbiology letters (FEMS Microbiol Lett) Vol. 352 Issue 1 Pg. 62-8 (Mar 2014) ISSN: 1574-6968 [Electronic] England
• PMID: 24383524 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Phenazines
• actinomycin G
• phenazinomycin
• Dactinomycin
• Methyltransferases

Topics

• Anti-Bacterial Agents (biosynthesis)
• Bacterial Proteins (genetics, metabolism)
• Biosynthetic Pathways
• Dactinomycin (biosynthesis)
• Gene Expression Regulation, Bacterial
• Gene Silencing
• Methyltransferases (genetics, metabolism)
• Molecular Sequence Data
• Multigene Family
• Phenazines (metabolism)
• Streptomyces (enzymology, genetics, metabolism)