ArticleSynthetic and systems biotechnology2027
Improved catalytic efficiency of P450 OleP for converting lithocholic acid into murideoxycholic and ursodeoxycholic acids through semi-rational and rational design.
Article in Synthetic and systems biotechnology, 2027. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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12 authors.
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Abstract
Cytochrome P450 enzymes are promising for synthesizing therapeutically beneficial bile acids murideoxycholic acid (MDCA) and ursodeoxycholic acid (UDCA) from lithocholic acid (LCA). However, the catalytic efficiency of P450 enzymes remains inadequate for large-scale production. Here, we address this limitation by engineering P450 OleP, achieving high activity for the efficient synthesis of MDCA and UDCA. Firstly, an improved high-throughput detection method for UDCA was developed to accelerate the screening process for mutants with improved UDCA synthesis capabilities. Next, the mutant S240A was generated through semi-rational design guided by the crystal structure of the OleP-LCA complex, resulting in an improvement in the MDCA conversion rate from 32.5% to 98.3% using 0.5 g L
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