Institute for Innovative Learning, Mahidol University, Nakhon Pathom, 73170, Thailand.
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong, 21210, Thailand.
Protein Sci. 2019 Jan;28(1):8-29. doi: 10.1002/pro.3525.
Many flavoenzymes catalyze hydroxylation of aromatic compounds especially phenolic compounds have been isolated and characterized. These enzymes can be classified as either single-component or two-component flavin-dependent hydroxylases (monooxygenases). The hydroxylation reactions catalyzed by the enzymes in this group are useful for modifying the biological properties of phenolic compounds. This review aims to provide an in-depth discussion of the current mechanistic understanding of representative flavin-dependent monooxygenases including 3-hydroxy-benzoate 4-hydroxylase (PHBH, a single-component hydroxylase), 3-hydroxyphenylacetate 4-hydroxylase (HPAH, a two-component hydroxylase), and other monooxygenases which catalyze reactions in addition to hydroxylation, including 2-methyl-3-hydroxypyridine-5-carboxylate oxygenase (MHPCO, a single-component enzyme that catalyzes aromatic-ring cleavage), and HadA monooxygenase (a two-component enzyme that catalyzes additional group elimination reaction). These enzymes have different unique structural features which dictate their reactivity toward various substrates and influence their ability to stabilize flavin intermediates such as C4a-hydroperoxyflavin. Understanding the key catalytic residues and the active site environments important for governing enzyme reactivity will undoubtedly facilitate future work in enzyme engineering or enzyme redesign for the development of biocatalytic methods for the synthesis of valuable compounds.
许多黄素酶催化芳香族化合物的羟化，特别是酚类化合物已被分离和鉴定。这些酶可以分为单组分或双组分黄素依赖羟化酶（单加氧酶）。该组酶催化的羟化反应可用于修饰酚类化合物的生物学性质。本文旨在深入讨论代表性黄素依赖单加氧酶的现有机制理解，包括 3-羟基苯甲酸 4-羟化酶（PHBH，单组分羟化酶）、3-羟基苯乙酸 4-羟化酶（HPAH，双组分羟化酶）和其他除羟化外还催化反应的单加氧酶，包括 2-甲基-3-羟基吡啶-5-羧酸氧酶（MHPCO，催化芳香环裂解的单组分酶）和 HadA 单加氧酶（催化其他基团消除反应的双组分酶）。这些酶具有不同的独特结构特征，决定了它们对各种底物的反应性，并影响它们稳定黄素中间体（如 C4a-过氧黄素）的能力。了解关键催化残基和对酶反应性起重要作用的活性位点环境，无疑将有助于未来的酶工程或酶重新设计工作，以开发生物催化方法合成有价值的化合物。
