Transacylation kinetics in fatty acid and polyketide synthases and its sensitivity to point mutations

  • Fatty acid and polyketide synthases (FASs and PKSs) synthesize physiologically and pharmaceutically important products by condensation of acyl building blocks. The transacylation reaction catalyzed by acyl transferases (ATs) is responsible for the selection of acyl-CoA esters for further processing by FASs and PKSs. In this study, the AT domains of different multidomain (type I) PKS systems are kinetically described in their substrate selectivity, AT−Acyl carrier protein (ACP) domain-domain interaction and enzymatic kinetic properties. We observe that the ATs of modular PKSs, intricate protein complexes occurring in bacteria and responsible for the biosynthesis of bioactive polyketides, are significantly slower than ATs of mammalian FASs, reflecting the respective purpose of the biosynthetic pathways within the organism and their metabolic context. We further perform a mutational study on the kinetics of the AT−ACP interaction in the modular PKS 6-deoxyerythronolide B synthase (DEBS) and find a high plasticity in enzyme properties, which we explain by a high plasticity in AT−ACP recognition. Our study enlarges the understanding of ATs in its molecular properties and is similarly a call for thorough AT-centered PKS engineering strategies.

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Author:Franziska Stegemann, Martin GriningerORCiDGND
Parent Title (English):ChemCatChem
Publisher:WILEY-VCH Verlag
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/03/04
Date of first Publication:2021/03/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/08/09
Tag:enzyme catalysis; enzyme kinetics; natural compound synthesis; protein engineering; protein-protein interactions
Page Number:12
First Page:2771
Last Page:2782
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Licence (German):License LogoCreative Commons - Namensnennung 4.0