Higher alcohols refer to alcohols containing three or more carbon atoms and represent an important class of chemicals widely used in various industries, such as fuels, solvents, coatings, and specialty chemicals. Traditionally, the production of these higher alcohols has depended heavily on petrochemical processes, which not only rely on non-renewable resources but also contribute significantly to environmental pollution. The finite nature of fossil fuels and the associated environmental concerns have prompted researchers to explore alternative, sustainable production methods. Consequently, the development of sustainable bio-based higher alcohol production technologies has emerged as a critical research focus. Recent advances in metabolic engineering and synthetic biology have paved the way for developing engineered microbial strains capable of producing higher alcohols through biological fermentation. By optimizing metabolic pathways, these engineered strains can channel more carbon flux toward the desired alcohol products. In addition, enhancing the tolerance of these strains to high concentrations of the produced alcohols and improving their overall biosynthetic capabilities are key strategies that have been successfully implemented. Such innovations have enabled the production of higher alcohols from renewable feedstocks in a more environmentally friendly and cost-effective manner. Renewable raw materials, such as lignocellulose, waste proteins, waste lipids, and carbon dioxide, provide diverse possibilities for the environmentally friendly and sustainable synthesis of higher alcohols. Lignocellulosic biomass, for instance, is abundant and renewable, making it an attractive alternative to conventional sugars. Waste proteins and lipids, often derived from industrial by-products, provide additional inexpensive substrates that not only help in waste valorization but also reduce the overall production cost. Carbon dioxide, as an abundant greenhouse gas, can be captured and converted into valuable higher alcohols, contributing to carbon sequestration and climate change mitigation. Despite these promising prospects, several challenges remain to be addressed. Issues such as low substrate conversion efficiency, the formation of inhibitory byproducts during fermentation, and high costs associated with downstream separation and purification continue to hinder commercial viability. This review provides a comprehensive overview of the current market size, major applications, and economic value of higher alcohols, with particular emphasis on the market performance of isobutanol, 1,3-butanediol, and 2,3-butanediol. In addition, the review explores the biosynthetic pathways utilized for higher alcohol production, including the acetyl-CoA-dependent pathway, the branched-chain amino acid synthesis pathway, and the fatty acid chain elongation pathway. It also summarizes key metabolic engineering strategies, such as cofactor balancing, competitive pathway elimination, enzyme optimization, and high-yield strain selection. Moreover, the utilization of extremophiles as chassis cells, in combination with next-generation industrial biotechnology (NGIB), represents a promising new direction for sustainable production. Looking ahead, the integration of biosensors, advanced gene editing technologies, and computer-aided metabolic engineering is expected to further optimize microbial cell factory design, thereby enhancing the industrial production efficiency of higher alcohols and promoting the development of renewable energy and green chemical industries. {L-End}
