Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I
Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I
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DOI：
10.1002/pro.3550
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发表时间：
2019-02-01
期刊：
影响因子：
8
通讯作者：
Grininger, Martin
中科院分区：
文献类型：
--
作者：
Rittner, Alexander;Paithankar, Karthik S.;Grininger, Martin
模块化是聚酮合酶（PKS）等大合酶的基本特性。在本研究中，我们利用 PKS 和动物脂肪酸合酶 (FAS) 之间的密切相似性来重新设计动物 FAS，以探讨 FAS/PKS 家族的模块化。在序列和结构信息的指导下，我们将动物 FAS 截断并解剖为其组件，并将它们重新组装以生成新的类似 PKS 的模块以及双模结构。新颖的重新设计模块类似于所有四种常见类型的 PKS，并证明这种方法可以成为提供具有更高催化效率的产品的强大工具。我们的数据例证了整个 FAS/PKS 折叠的固有可塑性和稳健性，并为探索基于 FAS 的生物合成途径进行定制化合物设计开辟了新途径。
Modularity is a fundamental property of megasynthases such as polyketide synthases (PKSs). In this study, we exploit the close resemblance between PKSs and animal fatty acid synthase (FAS) to re-engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by sequence and structural information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS-like modules as well as bimodular constructs. The novel re-engineered modules resemble all four common types of PKSs and demonstrate that this approach can be a powerful tool to deliver products with higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS-based biosynthetic pathways for custom compound design.