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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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