Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A.

Chemistry & Biology
Linquan BaiYi Yu

Abstract

A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VAL-A) biosynthesis revealed 16 structural genes, 2 regulatory genes, 5 genes related transport, transposition/integration or tellurium resistance; another 4 genes had no obvious identity. The VAL-A biosynthetic pathway was proposed, with assignment of the required genetic functions confined to the sequenced region. A cluster of eight reassembled genes was found to support VAL-A synthesis in a heterologous host, S. lividans 1326. In vivo inactivation of the putative glycosyltransferase gene (valG) abolished the final attachment of glucose for VAL production and resulted in accumulation of the VAL-A precursor, validoxylamine, while the normal production of VAL-A could be restored by complementation with valG. The role of valG in the glycosylation of validoxylamine to VAL-A was demonstrated in vitro by enzymatic assay.

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Citations

Jul 20, 2011·Journal of the American Chemical Society·Shumpei AsamizuTaifo Mahmud
Jun 30, 2012·Journal of the American Chemical Society·Shumpei AsamizuTaifo Mahmud
Jul 31, 2007·Journal of Natural Products·Taifo MahmudXiumei Wu
Aug 2, 2013·Molecular Plant-microbe Interactions : MPMI·Aurelien L CarlierLeo Eberl
Oct 1, 2013·BioMed Research International·Amit Kumar ChaudharyJae Kyung Sohng
Dec 3, 2014·Bioresource Technology·Tan-Che Zhou, Jian-Jiang Zhong
May 19, 2009·Journal of Biotechnology·Yueqiao LiaoJian-Jiang Zhong
Mar 27, 2009·Current Opinion in Chemical Biology·Taifo Mahmud
May 13, 2015·ELife·Andrew R OsbornTaifo Mahmud
Aug 16, 2016·Journal of Industrial Microbiology & Biotechnology·Jinsong FengWen-Wen Zhou
Jan 24, 2017·Bioscience, Biotechnology, and Biochemistry·Shumpei Asamizu
Mar 29, 2007·Natural Product Reports·Patricia M Flatt, Taifo Mahmud
Sep 3, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takuya Ito
Dec 30, 2006·Chembiochem : a European Journal of Chemical Biology·Xiumei WuTaifo Mahmud
Mar 6, 2007·Chembiochem : a European Journal of Chemical Biology·Kazuyuki MinagawaTaifo Mahmud
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