Biotechnology of isopentenols production from microbial cell factories

Isopentenols are a group of five-carbon branched alcohols, comprising positional isomers, isoprenol (3-methyl-3-buten-1-ol) and prenol (3-methyl-2-buten-1-ol). They have emerged as a versatile compound with applications spanning biotherapeutics, advanced biofuels, and nutraceuticals. Their favorable characteristics, including high energy density, fuel-blend compatibility, and demonstrated therapeutic potential, underscore their growing industrial and biomedical significance. Traditionally, isopentenols have been synthesized chemically or extracted from plants, but these methods are limited by environmental and economic constraints. Microbial production using engineered cell factories offers a sustainable alternative by harnessing the natural and/or synthetic routes to generate isoprenoid precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), from central metabolism. Diverse prokaryotic chassis, including Escherichia coli, Corynebacterium glutamicum, Vibrio natriegens, and Bacillus subtilis have been extensively engineered to optimize isopentenols production for diverse applications, from biofuel synthesis to nutraceutical development. Advances in metabolic engineering, synthetic biology, and fermentation strategies have significantly enhanced isopentenols yields from these microbial hosts. This review provides a comprehensive overview of microbial isopentenols production, focusing on genetic, transcriptional, and translational modifications, as well as culture condition optimization. Furthermore, innovative strategies involving alternative enzymes and live feedstocks are discussed. Key challenges such as pathway bottlenecks, host toxicity, and cost-effectiveness are critically evaluated to inspire future research in this promising field. To the best of our knowledge, this is the first review to comprehensively address all biotechnological aspects of microbial isopentenols production.