Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification

摘要: Flavoenzymes are ubiquitous in biological systems and catalyze a diverse range of chemical transformations. The flavoenzyme XiaK from the biosynthetic pathway indolosesquiterpene xiamycin A is demonstrated to mediate vivo biotransformation into multiple products, including chlorinated adduct as well dimers characterized by C–N N–N linkages that hypothesized form via radical-based mechanisms. Isolation characterization vitro shows it acts flavin-dependent N-hydroxylase catalyzes hydroxylation at carbazole nitrogen N-hydroxyxiamycin, product which was overlooked earlier experiments because its chromatographic properties similar those oxiamycin. N-Hydroxyxiamycin shown be unstable under aerobic conditions, electron paramagnetic resonance spectroscopy demonstrates formation an N-hydroxycarbazole radical adduct. This species proposed serve key intermediate leading adducts. study suggests non-enzyme catalyzed reactions may play greater role biosynthesis natural products than has been previously recognized.