Efficient Bioproduction of p-Hydroxybenzaldehyde β-Glucoside from p-Hydroxybenzaldehyde by Glycosyltransferase Mutant UGTBL1-Δ60

Lignin, as one of the three primary components of renewable lignocellulosic biomass, can be converted into aromatic platform chemicals and holds significant potential for high-value applications. <i>p</i>-Hydroxybenzaldehyde is a compound derived from lignin. In this study, the mutant Δ60 of the glycosyltransferase UGT_BL1 derived from <i>Bacillus licheniformis</i> was adopted to catalyze the glycosylation reaction of <i>p</i>-hydroxybenzaldehyde, producing a bioactive compound Helicid analogue (<i>p</i>-hydroxybenzaldehyde <i>β</i>-glucoside). Truncation mutations targeting loop regions may reduce local flexibility, thereby facilitating enhanced access of <i>p</i>-hydroxybenzaldehyde to the active site pocket and promoting relative activity. Under optimal conditions (35 °C, pH 7.5, and glucose 200 mM), a high yield of 97.8% for <i>p</i>-hydroxybenzaldehyde <i>β</i>-glucoside was achieved from 2 mM <i>p</i>-hydroxybenzaldehyde within 10 h. The conversion of 3 mM <i>p</i>-hydroxybenzaldehyde (366.4 mg/L) yielded up to 2.7 mM (767.5 mg/L) of <i>p</i>-hydroxybenzaldehyde <i>β</i>-glucoside within 48 h. According to the molecular docking results, the CDOCKER energy value of mutant Δ60 was lower than that of the wild-type, at -16.0 kcal/mol. To our knowledge, this is the first example of an efficient and environmentally sustainable approach for the synthesis of <i>p</i>-hydroxybenzaldehyde <i>β</i>-glucoside, providing a new insight for the valorization of lignin into valuable biobased chemicals.