Substrate-Specific Evolution of Amine Dehydrogenases for Accessing Structurally Diverse Enantiopure (R)-β-Amino Alcohols,ACS Catalysis

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Substrate-Specific Evolution of Amine Dehydrogenases for Accessing Structurally Diverse Enantiopure (R)-β-Amino Alcohols
ACS Catalysis ( IF 11.3 ) Pub Date : 2024-01-03 , DOI: 10.1021/acscatal.3c04995
Xinjian Yin _{1,

2} , Wenzhong Gong ₁ , Yujing Zeng ₁ , Hulin Qiu ₁ , Lan Liu _{1,

2} , Frank Hollmann ₃ , Bishuang Chen _{1,

2}

Affiliation

The biocatalytic oxidative deamination of β-amino alcohols holds significant practical potential in kinetic resolution and/or deracemization process to access (R)-β-amino alcohols. This study exemplifies a notable instance of acquisition and utilization of this valuable oxidative deamination activity. Initially, the mutation N261M (M0) was identified to endow a native valine dehydrogenase with oxidative deamination activity toward a few (S)-β-amino alcohols. Subsequently, a phylogenetic analysis-guided, double-code saturation mutagenesis strategy was proposed to engineer M0's side-chain binding site. This strategy facilitated the substrate-specific evolution of M0, resulting in the creation of a panel of mutants (M1–M4) with noteworthy oxidative deamination activity toward structurally diverse (S)-β-amino alcohols. Using these engineered amine dehydrogenases, termed as β-amino alcohol dehydrogenases (β-AADHs), the complete kinetic resolution and even deracemization of a range of β-amino alcohols have been achieved. This work reports distinct biocatalysts and a synthetic strategy for the synthesis of enantiopure (R)-β-amino alcohols and offers an innovative approach for substrate-specificity engineering of enzymes.

中文翻译：

胺脱氢酶的底物特异性进化，用于获取结构多样的对映体纯 (R)-β-氨基醇

β-氨基醇的生物催化氧化脱氨在动力学拆分和/或去消旋过程中获得( R )-β-氨基醇具有巨大的实际潜力。这项研究举例说明了获取和利用这种有价值的氧化脱氨活性的一个显着实例。最初，突变 N261M (M0) 被鉴定为赋予天然缬氨酸脱氢酶对一些 ( S )-β-氨基醇的氧化脱氨活性。随后，提出了一种以系统发育分析为指导的双密码饱和诱变策略来设计M0的侧链结合位点。这种策略促进了 M0 的底物特异性进化，从而产生了一组突变体 (M1-M4)，这些突变体对结构多样的 ( S )-β-氨基醇具有显着的氧化脱氨活性。使用这些被称为 β-氨基醇脱氢酶 (β-AADH) 的工程胺脱氢酶，可以实现一系列 β-氨基醇的完全动力学拆分甚至去消旋化。这项工作报告了独特的生物催化剂和合成对映体纯 ( R )-β-氨基醇的合成策略，并为酶的底物特异性工程提供了一种创新方法。

更新日期：2024-01-03

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