Towards sustainable long-chain dicarboxylic acid production: challenges and opportunities.

Long-chain dicarboxylic acids are versatile aliphatic compounds with two terminal carboxyl groups and hydrocarbon chains of 12 or more carbons, offering tunable thermal, mechanical, and chemical properties. They are widely used in polymers, lubricants, adhesives, pharmaceuticals, and other industrial chemicals. Conventional chemical synthesis relies on fossil feedstocks, harsh reagents, and energy-intensive processes, generating hazardous by-products and raising sustainability concerns. Microbial production has emerged as a greener alternative, exploiting α- and ω-oxidation pathways in oleaginous yeasts such as Candida viswanathii and Yarrowia lipolytica. Metabolic and process engineering—including β-oxidation disruption, cytochrome P450 overexpression, and optimized fed-batch cultivation—has improved titers and productivities. Renewable hydrophobic and hydrophilic feedstocks, including plant oils, lignocellulosic sugars, and industrial wastes, enhance sustainability. Beyond canonical LCDAs, enzymatic modifications enable the production of functionalized derivatives, including hydroxy fatty acids, α,ω-diols, α,ω-diamines, and amino carboxylic acids, broadening their applications in bio-based polymers. This mini review provides an overview of long-chain dicarboxylic acid production, covering chemical synthesis routes and microbial approaches. It focuses on microbial production strains, feedstock strategies, metabolic and process engineering, and the biosynthesis of LCDA derivatives as integrated approaches toward sustainable and industrially viable LCDA biomanufacturing.