Title
Evolution of the ThDP dependent pyruvate dehydrogenase E1 subunit for the conversion of long chain aliphatic ketoacids
Conference Dates
September 15-19, 2019
Abstract
Thiamine diphosphate (ThDP) dependent enzymes can catalyse the synthesis of chiral acyloins from both aldehydes and ketoacids as donor substrates, but the latter are generally preferred as they render the reaction under kinetic control.[1] While a large variety of aromatic aldehydes and polar donor substrates such as hydroxypyruvate and oxoglutarate are accepted by wild-type enzymes, the conversion of linear and branched chain aliphatic ketoacids remains a formidable challenge even after several rounds of directed evolution.[2] Due to its naturally large active site volume, the pyruvate dehydrogenase E1 subunit from E.coli (EcPDH E1) is a promising enzyme scaffold for directed evolution towards the conversion of sterically demanding, aliphatic ketoacids. Here we present initial results on the enzyme’s kinetic properties and its substrate scope.
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Recommended Citation
Stefan R. Marsden, Duncan G. G. McMillan, and Ulf Hanefeld, "Evolution of the ThDP dependent pyruvate dehydrogenase E1 subunit for the conversion of long chain aliphatic ketoacids" in "Enzyme Engineering XXV", Huimin Zhao, University of Illinois at Urbana-Champaign, USA John Wong, Pfizer, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/enzyme_xxv/25