Identification of novel tylosin analogues generated by a wblA disruption mutant of Streptomyces ansochromogenesReportar como inadecuado




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Microbial Cell Factories

, 14:173

First Online: 02 November 2015Received: 15 June 2015Accepted: 08 October 2015

Abstract

BackgroundStreptomyces, as the main source of antibiotics, has been intensively exploited for discovering new drug candidates to combat the evolving pathogens. Disruption of wblA, an actinobacteria-specific gene controlling major developmental transition, can cause the alteration of phenotype and morphology in many species of Streptomyces. One wblA homologue was found in Streptomyces ansochromogenes 7100 by using the Basic Local Alignment Search Tool. It is interesting to identify whether novel secondary metabolites could be produced by the wblA disruption mutant as evidenced in other Streptomyces.

ResultsThe wblA disruption mutant of S. ansochromogenes 7100 ΔwblA was constructed by homologous recombination. ΔwblA failed to produce spores and nikkomycin, the major product of S. ansochromogenes 7100 wild-type strain during fermentation. Antibacterial activity against Staphylococcus aureus and Bacillus cereus was observed with fermentation broth of ΔwblA but not with that of the wild-type strain. To identify the antibacterial compounds, the two compounds compound 1 and compound 2 produced by ΔwblA were characterized as 16-membered macrolides by mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical structure of these compounds shows similarity with tylosin, and the bioassays indicated that the two compounds inhibited the growth of a number of gram-positive bacteria. It is intriguing that they displayed much higher activity than tylosin against Streptococcus pneumoniae.

ConclusionsTwo novel tylosin analogues compound 1 and 2 were generated by ΔwblA. Bioassays showed that compound 1 and 2 displayed much higher activity than tylosin against Streptococcus pneumoniae, implying that these two compounds might be used to widen the application of tylosin.

KeywordswblA Nikkomycin Tylosin analogues Streptomyces ansochromogenes Bioassay Electronic supplementary materialThe online version of this article doi:10.1186-s12934-015-0359-5 contains supplementary material, which is available to authorized users.

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Autor: Cheng Lu - Guojian Liao - Jihui Zhang - Huarong Tan

Fuente: https://link.springer.com/



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