Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:
Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA; email:
Annu Rev Biochem. 2018 Jun 20;87:159-185. doi: 10.1146/annurev-biochem-062917-012042. Epub 2018 Mar 28.
Flavin-dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes have been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications.
黄素依赖型卤化酶(FDHs)通过协调还原黄素、分子氧和氯离子的反应,催化有机底物的卤化。这些酶的靶向和随机突变已被用于理解和改变它们的反应性。这些研究使我们深入了解了催化所必需的残基,以及具有提高稳定性、扩展底物范围和改变位点选择性的 FDH 变体。FDH 结构中的突变促成了所有这些进展。最近的研究旨在使这些突变对 FDH 功能的影响合理化,并确定新的 FDH,以加深我们对这一酶类的理解,并扩大它们在生物催化应用中的用途。