| Autor: |
Annaval T, Teijaro CN, Adhikari A, Yan X, Chen JJ, Crnovcic I, Yang D, Shen B |
| Jazyk: |
angličtina |
| Zdroj: |
ACS chemical biology [ACS Chem Biol] 2021 Jul 16; Vol. 16 (7), pp. 1172-1178. Date of Electronic Publication: 2021 Jun 17. |
| DOI: |
10.1021/acschembio.1c00365 |
| Abstrakt: |
Tiancimycin (TNM) A belongs to the anthraquinone-fused subfamily of enediyne natural products, and selected enediynes have been translated into clinical drugs. Previously, inactivation of tnmL in Streptomyces sp. CB03234 resulted in the accumulation of TNM B and TNM E, supporting the functional assignment of TnmL as a cytochrome P450 hydroxylase that catalyzes A-ring modification in TNM A biosynthesis. Herein, we report in vitro characterization of TnmL, revealing that (i) TnmL catalyzes two successive hydroxylations of TNM E, resulting in sequential production of TNM F and TNM C, (ii) TnmL shows a strict substrate preference, with the C-26 side chain playing a critical role in substrate binding, and (iii) TnmL demethylates the C-7 OCH 3 group of TNM G, affording TNM F, thereby channeling the shunt product TNM G back into TNM A biosynthesis and representing a rare proofreading logic for natural product biosynthesis. These findings shed new insights into anthraquinone-fused enediyne biosynthesis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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