Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I.

Autor: Rittner A; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, Frankfurt am Main, D-60438, Germany., Paithankar KS; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, Frankfurt am Main, D-60438, Germany., Drexler DJ; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, Frankfurt am Main, D-60438, Germany., Himmler A; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, Frankfurt am Main, D-60438, Germany., Grininger M; Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, Frankfurt am Main, D-60438, Germany.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2019 Feb; Vol. 28 (2), pp. 414-428. Date of Electronic Publication: 2018 Dec 20.
DOI: 10.1002/pro.3550
Abstrakt: 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.
(© 2018 The Protein Society.)
Databáze: MEDLINE
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