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Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
A Mechanism-Guided Strategy by Weighting Key Reaction States for Rational Engineering of ω-Transaminase toward Bulky
Lin Yang1,2, Xiaolan Sun3, Huilin Yang3
1Institute of Flow Chemistry and Engineering, College of Chemistry and Materials, Jiangxi Normal University, Nanchang 330022, China.
None:
A mechanism-guided strategy weighting two key reaction states, the prereaction conformation and external aldimine, enabled rational engineering of a novel ω-transaminase ATA-116 for bulky chiral amines. Two residues, W57F and R390S, were identified, showing 210- and 107-fold improvements in kcat/Km, respectively (>99% ee). The highest conversion reached 91% (2.5% for the wild type). The strategy also expanded the substrate scope across 15 indanone derivatives and improved thermostability. Molecular dynamics simulations elucidated the mechanistic basis.
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