PLP-independent racemization: mechanistic and mutational studies of O-ureidoserine racemase (DcsC)

Literature Information

Publication Date 2018-01-24
DOI 10.1039/C7OB03013D
Impact Factor 3.876
Authors

Yeong-Chan Ahn, Conrad Fischer, Marco J. van Belkum, John C. Vederas


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Abstract

O-Ureidoserine racemase (DcsC) is a PLP-independent enzyme in the biosynthetic route to the antibiotic D-cycloserine. Here we present the recombinant expression and characterization of a significantly more active DcsC variant featuring an N-terminal SUMO-tag. Synthesis of enantiomeric pure inhibitors in combination with site-specific mutation of active site cysteines to serines of this enzyme offers closer insights into the mechanism of this transformation. Homology modelling with a close relative (diaminopimelate epimerase, DapF) inspired C- and N-terminal truncation of DcsC to produce a more compact yet still active enzyme variant.

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Organic & Biomolecular Chemistry
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