Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A
Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A
复制标题
有效霉素生物合成基因簇的功能分析和有效羟胺 A 的工程化生产。
DOI:
10.1016/j.chembiol.2006.02.002
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发表时间:
2006-04-01
影响因子:
--
通讯作者:
Deng, ZX
中科院分区:
文献类型:
--
作者:
Bai, L;Li, L;Deng, ZX
A 45 kb DNA sequencing analysis from Streptomyces hygroscopicus 5008 involved in validamycin A (VALA) 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.