聚酮
聚酮合酶
酰基转移酶
化学
肟
立体化学
蛋白质工程
突变
模块化设计
酶
计算生物学
生物合成
生物化学
生物
基因
计算机科学
突变体
程序设计语言
作者
Hannah A. Minas,R François,Franziska Hemmerling,Amy E. Fraley,Cora Dieterich,Simon Rüdisser,Roy A. Meoded,Sabrina Collin,Kira J. Weissman,Arnaud Gruez,Jörn Piel
标识
DOI:10.1002/anie.202304481
摘要
Abstract Modular trans ‐acyltransferase polyketide synthases ( trans ‐AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis ‐AT counterparts, the trans ‐AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on‐line by an unusual oxygenase‐containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site‐directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein‐protein interactions that support this chemistry. Overall, our work adds oxime‐forming machinery to the biomolecular toolbox available for trans ‐AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides.
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