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Publication Abstract from PubMed

Aromatic polyketides are an important class of natural products with various bioactivities, and their structural diversity arises from modifications to their aromatic frameworks. In this study, we identify a stereoselective aromatase/cyclase (ARO/CYC) FasU, which is responsible for forming the axial chiral biphenyl framework in fasamycin. FasU catalyzes sequential decarboxylation and cyclization/aromatization with strict S-stereospecificity on a previously unidentified biosynthetic intermediate. Through crystal structure analysis and site-directed mutagenesis, we reveal the enzyme's substrate binding mode, stereospecificity, and the key residues involved in catalysis. This discovery introduces a novel class of ARO/CYC enzymes in type II polyketide biosynthesis, advancing the development of biocatalysts for chiral aromatic polyketides.

A Stereoselective Decarboxylative Aromatase/Cyclase Directs the Biosynthesis of an Axially Chiral Biphenyl Framework in Fasamycin.,Jiang K, Zhu C, Yan X, Li G, Lin Z, Deng Z, Luo S, Qu X J Am Chem Soc. 2025 Feb 19;147(7):5596-5601. doi: 10.1021/jacs.4c18376. Epub 2025 , Feb 6. PMID:39910892^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.