Baeyer-Villiger monooxygenases (BVMOs) are versatile biocatalysts for the conversion of ketones to lactones or esters while also being able to efficiently oxidize sulfides to sulfoxides. However, there are limitations for the application of BVMOs in synthesis. In this review we provide an overview of the protein engineering studies aiming at optimizing different properties of BVMOs. We describe hot spots in the active sites of certain BVMOs that have been successfully targeted for changing the substrate scope, as well as the possibility to influence this property by allosteric effects. The identified hot spots in the active sites for controlling enantio- and regioselectivity are shown to be transferable to other BVMOs and we describe concepts to influence heteroatom oxidation, improve protein stability and change the cofactor dependency of BVMOs. Summarizing all these different studies enabled the identification of BVMO- or property-dependent as well as universal hot spots.

Baeyer-Villiger单加氧酶（BVMO）是通用的生物催化剂，可将酮转化为内酯或酯，同时还能够有效地将硫化物氧化为亚砜。但是，BVMO在合成中的应用存在局限性。在这篇综述中，我们概述了旨在优化BVMOs不同特性的蛋白质工程研究。我们描述了某些BVMOs活性位点中的热点，这些热点已成功成为改变底物范围的目标，以及通过变构效应影响此特性的可能性。在控制对映和区域选择性的活性位点中确定的热点显示可转移到其他BVMOs，我们描述了影响杂原子氧化，改善蛋白质稳定性和改变BVMOs辅因子依赖性的概念。