Microbial generation of nocathiacin acid from nocathiacin I

Microbial generation of nocathiacin acid from nocathiacin I by manipulating enzymatic activities related to C-terminal dehydroalanine hydrolysis in Amycolatopsis fastidiosa LCB1001 was investigated by comparing the effects of various factors including metal ions, amino acid precursors and starting pH on the transformation. CuCl2 and cysteine significantly increased bioconversion yields, and starting pH and time were also major factors affecting the product yield. Under optimal conditions, the yield of nocathiacin acid was increased from 10.4 mg/L to greater than 45.0 mg/L after 6 days of fermentation. The use of protease inhibitors indicated that enzymes such as peptidylglycine monooxygenase and alcylase I are likely involved in the bioconversion. This is the first report on the generation of nocathiacin acid through microbial conversion in situ. Compared to chemical methods, the present approach is more effective and could be broadly applied in the production of novel derivatives of microbial secondary metabolites.