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Title 

Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the pikD regulatory gene in Streptomyces Venezuelae

Authors 

W S JungS J JeongS R ParkC Y ChoiByoung Chul ParkJ W ParkY J Yoon

Publisher 

American Society for Microbiology

Issue Date 

2008

Citation 

Applied and Environmental Microbiology, vol. 74, no. 7, pp. 1972-1979

Keywords 

gene expressionmutagenesisdesosaminyl macrolideshydroxylated derivativesstreptomyces venezuelaedesosaminyl tylactonelactone derivativeprotein derivativegene cluster

Abstract 

To elevate the production level of heterologous polyketide in Streptomyces venezuelae, an additional copy of the positive regulatory gene pikD was introduced into the pikromycin (Pik) polyketide synthase (PKS) deletion mutant of S. venezuelae ATCC 15439 expressing tylosin PKS genes. The resulting mutant strain showed enhanced production of both tylactone (TL) and desosaminyl tylactone (DesTL) of 2.7- and 17.1-fold, respectively. The notable increase in DesTL production strongly suggested that PikD upregulates the expression of the desosamine (des) biosynthetic gene cluster. In addition, two hydroxylated forms of DesTL were newly detected from the extract of this mutant. These hydroxylated forms presumably resulted from a PikD-dependent increase in expression of the pikC gene that encodes P450 hydroxylase. Gene expression analysis by reverse transcriptase PCR and bioconversion experiments of 10-deoxymethynolide, narbonolide, and TL into the corresponding desosaminyl macrolides indicated that PikD is a positive regulator of the des and pikC genes, as well as the Pik PKS genes. These results demonstrate the role of PikD as a pathway-specific positive regulator of the entire Pik biosynthetic pathway and its usefulness in the development of a host-vector system for efficient heterologous production of desosaminyl macrolides and novel hydroxylated compounds.

ISSN 

0099-2240

Link 

http://dx.doi.org/10.1128/AEM.02296-07

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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