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Numerous bacteria from different phylae can perform desulfurization reactions of organosulfur compounds. In these degradation or detoxification pathways, two-component flavin-dependent monooxygenases that use flavins (FMN or FAD) as a cofactor play important roles as they catalyse the first steps of these metabolic routes. The TdsC or DszC and MsuC proteins belong to this class of enzymes as they process dibenzothiophene (DBT) and methanesulfinate. Elucidation of their X-ray structures in apo, ligand-bound and cofactor-bound forms has provided important molecular insights into their catalytic reaction. Mycobacterial species have also been shown to possess a DBT degradation pathway, but no structural information is available on these two-component flavin-dependent monooxygenases. In this study, the crystal structure of the uncharacterized MAB_4123 protein from the human pathogen Mycobacterium abscessus is presented. The structure solved at high resolution displays high similarity to homologs from Rhodococcus, Paenibacillus and Pseudomonas species. In silico docking approaches suggest that MAB_4123 binds FMN and may use it as a cofactor. Structural analysis strongly suggests that MAB_4123 is a two-component flavin-dependent monooxygenase that could act as a detoxifying enzyme of organosulfur compounds in mycobacteria.
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http://dx.doi.org/10.1107/S2053230X2300345X | DOI Listing |
bioRxiv
August 2025
Department of Chemistry and Biochemistry, College of Natural Sciences and Mathematics, The University of Toledo, 2801 W. Bancroft St, Toledo, OH, 43606, U.S.A.
BorF is a short-chain flavin reductase from a desert soil bacterium that uses NADH to reduce FAD to FADH, which is used by the tryptophan-6-halogenase BorH to chlorinate tryptophan in the biosynthetic pathway of borregomycin A. The X-ray crystal structure of BorF bound to FAD was solved to 2.37 Å by molecular replacement and consists of a homodimer of single-domain protomers with a Greek key split β-barrel topology containing a domain-swapped N-terminal α-helix, as seen in other members of this family.
View Article and Find Full Text PDFAppl Environ Microbiol
August 2025
Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Key Laboratory of Agricultural and Environmental Microbiology, Ministry of Agriculture and Rural Affairs, Nanjing, Jiangsu, China.
Isoprocarb (IPC), a widely used carbamate insecticide, causes environmental contamination and poses risks to humans and ecosystems. sp. D-6, capable of utilizing IPC as the sole growth substrate, was isolated by our lab.
View Article and Find Full Text PDFJ Biol Chem
February 2025
Structural Biochemistry, Department of Chemistry, Bielefeld University, Bielefeld, Germany. Electronic address:
Two-component flavin-dependent monooxygenases are of great interest as biocatalysts for the production of pharmaceuticals and other relevant molecules, as they catalyze chemically important reactions such as hydroxylation, epoxidation, and halogenation. The monooxygenase components require a separate flavin reductase which provides the necessary reduced flavin cofactor. The tryptophan halogenase Thal from Streptomyces albogriseolus is a well-characterized two-component flavin-dependent halogenase.
View Article and Find Full Text PDFRSC Chem Biol
January 2025
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC) Wangchan Valley Rayong Thailand
Understanding how an enzyme regulates its function through substrate or allosteric regulation is crucial for controlling metabolic pathways. Some flavin-dependent monooxygenases (FDMOs) have evolved an allosteric mechanism to produce reduced flavin while minimizing the use of NADH and the production of harmful hydrogen peroxide (HO). In this work, we investigated in-depth mechanisms of how the reductase component (C1) of -hydroxyphenylacetate (HPA) 3-hydroxylase (HPAH) from is allosterically controlled by the binding of HPA, which is a substrate of its monooxygenase counterpart (C2).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Department of Chemistry, University of Massachusetts, Boston, MA 02125.
Sulfur is an essential element for life. Bacteria can obtain sulfur from inorganic sulfate; but in the sulfur starvation-induced response, employ two-component flavin-dependent monooxygenases (TC-FMOs) from the and operons to assimilate sulfur from environmental compounds including alkanesulfonates and dialkylsulfones. Here, we report binding studies of oxidized FMN to enzymes involved within the enzymatic pathway responsible for converting dimethylsulfone (DMSO) to sulfite.
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