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Enhanced production of hydroxylated macrolides from the pikromycin pathway of Streptomyces venezuelae

Paper ID Volume ID Publish Year Pages File Format Full-Text
18519 42725 2006 5 PDF Available
Title
Enhanced production of hydroxylated macrolides from the pikromycin pathway of Streptomyces venezuelae
Abstract

The post-PKS (polyketide synthase) modification reactions, including the hydroxylation step catalyzed by cytochrome P450 monooxygenases, are often crucial to the structural diversity and biological potency of the macrolide polyketides. In this study, we describe a strategy for enhancing the productivity of a set of desired hydroxylated macrolides. In a liquid culture of Streptomyces venezuelae, the intermediate macrolides, YC-17 and narbomycin, accumulate, and a small amount of hydroxylated compounds, namely neomethymycin and pikromycin, is produced. The improved generation of hydroxylated polyketides mediated by the PikC cytochrome hydroxylase from S. venezuelae was accomplished via the overexpression of the pikC gene, the supplementation of ferrous sulfate into the liquid medium, and feeding with the aglycones, 10-deoxymethynolide and narbonolide. In particular, this enhancement of production was achieved with a considerable reduction in culture time. In a liquid culture of a mutant strain (YJ029) that overexpresses the pikC gene, the bioconversion of the 12-membered ring macrolide YC-17 to methymycin and neomethymycin increased by approximately three-fold as compared to that of wild-type S. venezuelae. In the case of the 14-membered ring macrolide, narbomycin, bioconversion to pikromycin increased by approximately five-fold. In addition, the addition of ferrous sulfate and the feeding of aglycones into the medium resulted in a significantly higher generation of the desired hydroxylated macrolides.

Keywords
Hydroxylated macrolide polyketide; Post-PKS modification; Streptomyces venezuelae; PikC cytochrome P450
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Enhanced production of hydroxylated macrolides from the pikromycin pathway of Streptomyces venezuelae
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Publisher
Database: Elsevier - ScienceDirect
Journal: Enzyme and Microbial Technology - Volume 39, Issue 4, 2 August 2006, Pages 778–782
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us