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Abstract Flavin-dependent halogenases (FDHs) are a class of enzymes renowned for their regioselective ability to precisely insert halogen atoms into small aromatic compounds. Halogen incorporation can enhance the physicochemical and biological properties of molecules, making them valuable for agrochemical and pharmaceutical applications. Through bioinformatic mining of bacterial genomes, we discovered and functionally characterized SnFDHal, an efficient tryptophan 5-halogenase fromStreptomyces nourseiNRRL B-1714. This halogenase operates across a broad pH range and exhibits a melting temperature of 46.7 °C at both pH 6 and pH 8, which is comparable to thermophilic halogenases such as Th-Hal and BorH, and notably higher than those of mesophilic counterparts. Steady-state kinetic analysis revealed that SnFDHal displays superior catalytic efficiency for the chlorination of L-tryptophan compared to other FDHs reported to date. Structural modeling of its active site suggests that a conserved bulky phenylalanine residue (F49) promotes halogenation at the C-5 position of L-tryptophan, consistent with experimental findings. The combination of high catalytic efficiency and thermostability positions SnFDHal as a promising biocatalyst for applications in agrochemical and pharmaceutical industries.
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Using Small Molecules to Enhance P450 OleT Enzyme Activity in Situ
Abstract Cytochrome P450 OleT is a fatty acid decarboxylase that catalyzes the production of olefins with biofuel and synthetic applications. However, the relatively sluggish catalytic efficiency of the enzyme limits its applications. Here, we report the application of a novel class of benzene containing small molecules to improve the OleT activity. The UV‐Vis spectroscopy study and molecular docking results confirmed the high proximity of the small molecules to the heme group of OleT. Up to 6‐fold increase of product yield has been achieved in the small molecule‐modulated enzymatic reactions. Our work thus sheds the light to the application of small molecules to increase the OleT catalytic efficiency, which could be potentially used for future olefin productions.
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- Award ID(s):
- 1655740
- PAR ID:
- 10230216
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 27
- Issue:
- 35
- ISSN:
- 0947-6539
- Format(s):
- Medium: X Size: p. 8940-8945
- Size(s):
- p. 8940-8945
- Sponsoring Org:
- National Science Foundation
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