Journal
CHEMISTRY & BIOLOGY
Volume 13, Issue 4, Pages 387-397Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2006.02.002
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Funding
- ARRA NIH HHS [RA061528A] Funding Source: Medline
- NIAID NIH HHS [R01 AI061528] Funding Source: Medline
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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.
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