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Publication Abstract from PubMed

Aromatic-fused gamma-pyrones are structural features of many bioactive natural products and valid scaffolds for medicinal chemistry. However, the enzymology of their formation has not been completely established. Now it is demonstrated that TxnO9, a CalC-like protein belonging to a START family, functions as an unexpected anthraquinone-gamma-pyrone synthase involved in the biosynthesis of antitumor antibiotic trioxacarcin A (TXN-A). Structural analysis by NMR identified a likely substrate/product-binding mode and putative key active sites of TxnO9, which allowed an enzymatic mechanism to be proposed. Moreover, a subset of uncharacterized homologous proteins bearing an unexamined Lys-Thr dyad exhibit the same function. Therefore, the functional assignment and mechanistic investigation of this gamma-pyrone synthase elucidated an undescribed step in TXN-A biosynthesis, and the discovery of this new branch of polyketide heterocyclases expands the functions of the START superfamily.

Enzymology of Anthraquinone-gamma-Pyrone Ring Formation in Complex Aromatic Polyketide Biosynthesis.,Hou XF, Song YJ, Zhang M, Lan W, Meng S, Wang C, Pan HX, Cao C, Tang GL Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13475-13479. doi:, 10.1002/anie.201806729. Epub 2018 Sep 19. PMID:30151879^[1]

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