Structural Characterization and Extended Substrate Scope Analysis of Two Mg2+-Dependent O-Methyltransferases from Bacteria**

Autor: Nika Sokolova, Lili Zhang, Sadaf Deravi, Rick Oerlemans, Matthew R. Groves, Kristina Haslinger
Přispěvatelé: Chemical and Pharmaceutical Biology, Drug Design, Medicinal Chemistry and Bioanalysis (MCB), Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: ChemBioChem, 24(9):e202300076. WILEY-V C H VERLAG GMBH
ChemBioChem
ISSN: 1439-4227
Popis: Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by 15 O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for 16 sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we 17 characterized two bacterial OMTs from Desulforomonas acetoxidans and Streptomyces avermitilis in 18 terms of their enzymatic properties and substrate scope and determined their crystal structures. Both 19 OMTs methylated a wide range of catechol-like substrates, including flavonoids, coumarins, 20 hydroxybenzoic acids and their respective aldehydes, an anthraquinone and an indole. One enzyme also 21 accepted a steroid. The product range included pharmaceutically relevant compounds such as 22 (iso)fraxidin, iso(scopoletin), chrysoeriol, alizarin 1-methyl ether and 2-methoxyestradiol. Interestingly, 23 certain non-catechol flavonoids and hydroxybenzoic acids were also methylated. This study expands the 24 knowledge on substrate preference and structural diversity of bacterial catechol OMTs and paves the way 25 for their use in (combinatorial) pathway engineering.
Databáze: OpenAIRE
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