通过打破 sp. AK1 BBOX 中“芳香笼”的空间限制实现新型小分子醇的合成。

New small-molecule alcohol synthesis by breaking the space limitation of the "aromatic cage" in sp. AK1 BBOX.

机构信息

School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi Province 030001, China.

College of Chemistry & Molecular Science, Wuhan University, Wuhan, Hubei Province 430072, China.

出版信息

Org Biomol Chem. 2023 Aug 9;21(31):6397-6404. doi: 10.1039/d3ob00830d.

DOI:10.1039/d3ob00830d

PMID:37497645

Abstract

Fe(II)/2OG-dependent oxygenase γ-butyrobetaine hydroxylase (BBOX) stereoselectively hydroxylates inactive C-H bonds and produces L-carnitine. It has potential applications in the biosynthesis of L-carnitine and the synthesis of other small molecule alcohols. In this paper, we systematically explore the substrate range of sp. AK1 BBOX (psBBOX), with emphasis on the quaternary ammonium portion of γ-butyrobetaine (γ-BB). The space limitation of the "aromatic cage" in psBBOX in the hydroxylation of large quaternary ammonium analogues was studied, and the role of four aromatic amino acid residues in the substrate binding mode was analyzed. Consequently, the F188A mutant was developed with the ability to hydroxylate cyclic quaternary ammonium analogues and generate new alcohol compounds by breaking the limitation of the "aromatic cage".

摘要

Fe(II)/2OG 依赖性加氧酶 γ-丁基甜菜碱羟化酶（BBOX）立体选择性地羟基化非活性 C-H 键，生成 L-肉碱。它在 L-肉碱的生物合成和其他小分子醇的合成中有潜在的应用。在本文中，我们系统地研究了 sp. AK1 BBOX（psBBOX）的底物范围，重点是 γ-丁基甜菜碱（γ-BB）的季铵部分。研究了 psBBOX 中环状季铵类似物在羟化过程中“芳构性笼”的空间限制，并分析了四个芳香族氨基酸残基在底物结合模式中的作用。因此，开发了 F188A 突变体，它能够羟化环状季铵类似物，并通过打破“芳构性笼”的限制生成新的醇化合物。