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An unexpected role of EasDaf: catalyzing the conversion of chanoclavine aldehyde to chanoclavine acid.
- Source :
- Applied Microbiology & Biotechnology; 5/7/2024, Vol. 108 Issue 1, p1-10, 10p
- Publication Year :
- 2024
-
Abstract
- Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasD<subscript>af</subscript> or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasD<subscript>af</subscript> not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. Key points: •EAs possess complicated skeletons and are widely used in several clinical diseases •EasD<subscript>af</subscript>belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid •The catalytic mechanism of EasD<subscript>af</subscript>for dehydrogenation was analyzed by molecular docking and site mutations [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01757598
- Volume :
- 108
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Applied Microbiology & Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 177079433
- Full Text :
- https://doi.org/10.1007/s00253-024-13157-8