Structural highlights
Publication Abstract from PubMed
Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final alpha-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant. The X-ray crystal structures of ChaP and two homologues, docking studies, and site-directed mutagenesis provided insights into the molecular basis of the oxidative rearrangement that involves two successive C-C bond cleavage steps followed by lactonization. ChaP is the first example of a dioxygenase that requires a flavin-activated oxygen as a substrate despite lacking flavin binding sites, and represents a new class in the vicinal oxygen chelate enzyme superfamily.
Molecular Basis for the Final Oxidative Rearrangement Steps in Chartreusin Biosynthesis.,Wang YS, Zhang B, Zhu J, Yang CL, Guo Y, Liu CL, Liu F, Huang H, Zhao S, Liang Y, Jiao RH, Tan RX, Ge HM J Am Chem Soc. 2018 Aug 15. doi: 10.1021/jacs.8b06623. PMID:30067334[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang YS, Zhang B, Zhu J, Yang CL, Guo Y, Liu CL, Liu F, Huang H, Zhao S, Liang Y, Jiao RH, Tan RX, Ge HM. Molecular Basis for the Final Oxidative Rearrangement Steps in Chartreusin Biosynthesis. J Am Chem Soc. 2018 Aug 15. doi: 10.1021/jacs.8b06623. PMID:30067334 doi:http://dx.doi.org/10.1021/jacs.8b06623
