Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification.

Autor: Yang D, Ye F, Teijaro CN, Hwang D, Annaval T, Adhikari A, Li G, Yan X, Gui C, Rader C, Shen B
Jazyk: angličtina
Zdroj: Organic letters [Org Lett] 2022 Feb 11; Vol. 24 (5), pp. 1219-1223. Date of Electronic Publication: 2022 Jan 27.
DOI: 10.1021/acs.orglett.2c00009
Abstrakt: Comparative analyses of four anthraquinone-fused enediyne biosynthetic gene clusters (BGCs) identified YpmL as a cytochrome P450 enzyme unique to the yangpumicin (YPM) BGC. In vitro characterization of YpmL established it as a hydroxylase, catalyzing C-6 hydroxylation in YPM A biosynthesis. In vivo application of YpmL enabled engineered production of four new tiancimycin analogues ( 14 - 17 ). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure-activity relationship.
Databáze: MEDLINE