Abstract
NAD(H)/NADP(H)-dependent aldehyde/alcohol oxidoreductase (AAOR) participates in a wide range of physiologically important cellular processes by reducing aldehydes or oxidizing alcohols. Among AAOR substrates, furan aldehyde is highly toxic to microorganisms. To counteract the toxic effect of furan aldehyde, some bacteria have evolved AAOR that converts furan aldehyde into a less toxic alcohol. Based on biochemical and structural analyses, we identified Bacillus subtilis YugJ as an atypical AAOR that reduces furan aldehyde. YugJ displayed high substrate specificity toward 5-hydroxymethylfurfural (HMF), a furan aldehyde, in an NADPH- and Ni2+-dependent manner. YugJ folds into a two-domain structure consisting of a Rossmann-like domain and an α-helical domain. YugJ interacts with NADP and Ni2+ using the interdomain cleft of YugJ. A comparative analysis of three YugJ structures indicated that NADP(H) binding plays a key role in modulating the interdomain dynamics of YugJ. Noticeably, a nitrate ion was found in proximity to the nicotinamide ring of NADP in the YugJ structure, and the HMF-reducing activity of YugJ was inhibited by nitrate, providing insights into the substrate-binding mode of YugJ. These findings contribute to the characterization of the YugJ-mediated furan aldehyde reduction mechanism and to the rational design of improved furan aldehyde reductases for the biofuel industry.
Highlights
NAD(H)/NADP(H)-dependent aldehyde/alcohol oxidoreductase (AAOR) catalyzes aldehyde reduction or alcohol oxidation [1]
Each AAOR exhibits a unique substrate specificity depending on its physiological role, it generally reacts with multiple types of aldehydes or alcohols [13,16,17]
These observations indicate that YugJ functions as a furan aldehyde reductase rather than as an alcohol dehydrogenase
Summary
NAD(H)/NADP(H)-dependent aldehyde/alcohol oxidoreductase (AAOR) catalyzes aldehyde reduction or alcohol oxidation [1]. Each AAOR exhibits a unique substrate specificity depending on its physiological role, it generally reacts with multiple types of aldehydes or alcohols [13,16,17]. Both Escherichia coli YqhD and Thermotoga hypogea AAOR were active toward a wide range of aldehydes [16,18]. Because of its detoxification activity, furan aldehyde-reducing AAOR can be applied to the biofuel industry, in which fuel ethanol is obtained via the microbial fermentation of lignocellulosic biomass [28,29]. B. subtilis is an atypical NADPH-dependent group III AAOR that reduces furan aldehyde in the presence of a Ni2+ cofactor.
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