TY  - JOUR
A1  - Stegemann, Franziska
A1  - Grininger, Martin
T1  - Transacylation kinetics in fatty acid and polyketide synthases and its sensitivity to point mutations
T2  - ChemCatChem
N2  - 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.
KW  - enzyme catalysis
KW  - enzyme kinetics
KW  - natural compound synthesis
KW  - protein engineering
KW  - protein-protein interactions
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61900
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-619003
SN  - 1867-3899
VL  - 13
IS  - 12
SP  - 2771
EP  - 2782
PB  - WILEY-VCH Verlag
CY  - Weinheim
ER  -