On the Mechanisms of Hypohalous Acid Formation and Electrophilic Halogenation by Non-Native Halogenases.

Enzymatic electrophilic halogenation is a mild tool for functionalization of diverse organic compounds. Only a few groups of native halogenases are capable of catalyzing such a reaction. In this study, we used a mechanism-guided strategy to discover the electrophilic halogenation activity catalyzed by non-native halogenases.

Unifying and versatile features of flavin-dependent monooxygenases: Diverse catalysis by a common C4a-(hydro)peroxyflavin.

Flavin-dependent monooxygenases (FDMOs) are known for their remarkable versatility and for their crucial roles in various biological processes and applications. Extensive research has been conducted to explore the structural and functional relationships of FDMOs. The majority of reported FDMOs utilize C4a-(hydro)peroxyflavin as a reactive intermediate to incorporate an oxygen atom into a wide range of compounds.

Enzymes, Biocatalysis, and Metabolic Engineering for Enabling a Circular Economy and Sustainability.

Since the industrial revolution, the rapid growth and development of global industries have depended largely upon the utilization of coal-derived chemicals, and more recently, the utilization of petroleum-based chemicals. These developments have followed a linear economy model (produce, consume, and dispose). As the world is facing a serious threat from the climate change crisis, a more sustainable solution for manufacturing, i.

Dissecting the low catalytic capability of flavin-dependent halogenases.

Although flavin-dependent halogenases (FDHs) are attractive biocatalysts, their practical applications are limited because of their low catalytic efficiency. Here, we investigated the reaction mechanisms and structures of tryptophan 6-halogenase (Thal) from Streptomyces albogriseolus using stopped-flow, rapid-quench flow, quantum/mechanics molecular mechanics calculations, crystallography, and detection of intermediate (hypohalous acid [HOX]) liberation. We found that the key flavin intermediate, C4a-hydroperoxyflavin (C4aOOH-FAD), formed by Thal and other FDHs (tryptophan 7-halogenase [PrnA] and tryptophan 5-halogenase [PyrH]), can react with I, Br, and Cl but not F to form C4a-hydroxyflavin and HOX.

Structures, mechanisms and applications of flavin-dependent halogenases.

Overall, this review highlights the structures, mechanisms and applications of flavin-dependent halogenases (FDHs) for future development of FDHs as potential biocatalysts. FDHs catalyze incorporation of halogen atoms into a broad range of substrates. The reactions involved in the production of various halogenated natural products which are important drugs.