Hot spots for the protein engineering of Baeyer-Villiger monooxygenases

被引:79
作者
Balke, Kathleen [1 ]
Beier, Andy [1 ]
Bornscheuer, Uwe T. [1 ]
机构
[1] Greifswald Univ, Dept Biotechnol & Enzyme Catalysis, Inst Biochem, D-17487 Greifswald, Germany
关键词
Baeyer-Villiger monooxygenase; Protein engineering; Hot spots; Enantioselectivity; Substrate scope; Regioselectivity; Heteroatom oxidation; Cofactor usage; Uncoupling; Protein stability; P-HYDROXYBENZOATE HYDROXYLASE; KETOL-ACID REDUCTOISOMERASES; ENZYME CASCADE SYNTHESIS; BETA-AMINO ALCOHOLS; CYCLOHEXANONE MONOOXYGENASE; DIRECTED EVOLUTION; PHENYLACETONE-MONOOXYGENASE; COENZYME SPECIFICITY; THERMOBIFIDA-FUSCA; ACTIVE-SITE;
D O I
10.1016/j.biotechadv.2017.11.007
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 regios-electivity 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.
引用
收藏
页码:247 / 263
页数:17
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