nerol

Nerol is an acyclic monoterpene alcohol and a natural product that acts as a valuable flavor ingredient. It exhibits biological activity as an antimicrobial agent, showing inhibitory effects against the fungi Aspergillus niger, Aspergillus flavus, and the yeast Candida albicans. Structurally, nerol is synthesized from C10 prenyl diphosphate precursors through dephosphorylation reactions starting with substrate ionization and ending with water addition [284].

The de novo microbial biosynthesis of nerol is achieved by co-optimizing the upstream precursor supply and downstream enzymatic conversion steps. To supply the essential neryl diphosphate (NPP) precursor, which is orthogonal to native growth-associated pathways, metabolic engineering strategies overproduce the common isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through an optimized heterologous mevalonate (MVA) pathway. Downstream conversion is directed by the heterologous expression of a truncated neryl diphosphate synthase (such as SltNPPS from Solanum lycopersicum) coupled with a nerol synthase (such as GmNES from Glycine max). Furthermore, the dephosphorylation of the C10 intermediate to the final terpene alcohol can be driven by the overexpression of endogenous Nudix hydrolases, particularly NudJ, which demonstrates high hydrolytic activity toward neryl diphosphate. To manage product volatility and alleviate the toxicity of accumulated monoterpene alcohols, which can damage cell membranes, a two-phase fermentation system using an organic overlay like isopropyl myristate is employed for in situ product extraction [284].