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An FAD-Dependent Pyridine Nucleotide-Disulfide Oxidoreductase Is Involved in Disulfide Bond Formation in FK228 Anticancer Depsipeptide
- Source :
-
Chemistry & Biology . Jun2009, Vol. 16 Issue 6, p585-593. 9p. - Publication Year :
- 2009
-
Abstract
- Summary: Disulfide bonds are rare in bacterial natural products, and the mechanism of disulfide bond formation in those products is unknown. Here we characterize a gene and its product critical for a disulfide bond formation in FK228 anticancer depsipeptide in Chromobacterium violaceum. Deletion of depH drastically reduced FK228 production, whereas complementation of the depH-deletion mutant with a copy of depH on a medium copy-number plasmid not only fully restored the FK228 production but also significantly increased the FK228 yield. Purified 6xHis-tagged DepH fusion protein in native form is a homodimer of 71.0 kDa, with each monomer containing one molecule of FAD. DepH efficiently converts an immediate FK228 precursor to FK228 in the presence of NADP+. We conclude that DepH is an FAD-dependent pyridine nucleotide-disulfide oxidoreductase, specifically and efficiently catalyzing a disulfide bond formation in FK228. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 10745521
- Volume :
- 16
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Chemistry & Biology
- Publication Type :
- Academic Journal
- Accession number :
- 42966302
- Full Text :
- https://doi.org/10.1016/j.chembiol.2009.05.005