Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I. (20th December 2018)

• Record Type: Journal Article
• Authors: Rittner, Alexander; Paithankar, Karthik S.; Drexler, David Jan; Himmler, Aaron; Grininger, Martin
• Is Part Of: Protein science. Volume 28:Number 2(2019)
• Page Start: 414
• Page End: 428
• Publication Date: 2018-12-20
• Subjects: multidomain protein -- modularity of megasynthases -- polyketide synthase -- protein engineering -- fatty acid synthase; Proteins -- Periodicals; 572.6
• DOI: 10.1002/pro.3550
• Languages: English
• ISSNs: 0961-8368

Abstract

Abstract: 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.