Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents,Angewandte Chemie International Edition

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Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2023-05-23 , DOI: 10.1002/anie.202304476
Eveline Vriens _{1,

2} , Dries De Ruysscher _{1,

2} , Angus N M Weir _{1,

2} , Sofie Dekimpe _{1,

2} , Gert Steurs ₃ , Ahmed Shemy ₄ , Leentje Persoons ₅ , Ana Rita Santos ₆ , Christopher Williams ₇ , Dirk Daelemans ₅ , Matthew P Crump ₇ , Arnout Voet ₄ , Wim De Borggraeve ₈ , Eveline Lescrinier ₉ , Joleen Masschelein _{1,

2}

Affiliation

The anticancer agent oximidine I and three novel variants were discovered as products of a cryptic trans-AT PKS/NRPS in Pseudomonas baetica. By manipulating the biosynthetic pathway, a key intermediate was identified that retains potent anticancer properties. A combination of bioinformatics analysis and genetic and biochemical experiments illuminated the oximidine biosynthetic pathway, including a novel mechanism for O-methyloxime formation.

中文翻译：

肟胺抗癌剂生物合成中聚酮合酶介导的 O-甲基肟形成

抗癌剂肟脒 I 和三种新变体被发现是细菌假单胞菌中隐秘的反式AT PKS/NRPS的产物。通过操纵生物合成途径，发现了一种保留有效抗癌特性的关键中间体。生物信息学分析与遗传和生化实验相结合，阐明了肟胺生物合成途径，包括O-甲基肟形成的新机制。

更新日期：2023-05-23

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