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Construction of a Highly Diastereoselective Aldol Reaction System with l-Threonine Aldolase by Computer-Assisted Rational Molecular Modification and Medium Engineering.

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Diastereoselectivity of l-threonine aldolase (LTA) was determined by paths of aldehydes attacking a pyridoxal phosphate-glycine complex. Thus, strategies of enhancing the syn path and blocking the anti path were performed… Click to show full abstract

Diastereoselectivity of l-threonine aldolase (LTA) was determined by paths of aldehydes attacking a pyridoxal phosphate-glycine complex. Thus, strategies of enhancing the syn path and blocking the anti path were performed to modify LTA. A mutant (Y31H/N305R) was constructed with a substrate preference increase from 3.32 to 42.04. Medium engineering was investigated. Consequently, the de value of l-syn-3-[4-(methylsulfonyl)phenylserine] reached 93.1% (87.2%conv). The study clarified the factors affecting diastereoselectivity of LTA and provided a theorem for rational modification of LTA's diastereoselectivity.

Keywords: threonine aldolase; lta; medium engineering

Journal Title: Organic letters
Year Published: 2020

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