Sustainable Biotechnological Production of Citronellol: Advances in Biosynthesis, Metabolic Engineering, and Applications

Citronellol is a naturally occurring acyclic monoterpene alcohol found in essential oils of aromatic plants such as Pelargonium graveolens, Rosa spp., and Cymbopogon nardus. Known for its pleasant rose-like aroma, citronellol has gained attention for its diverse industrial and pharmacological applications, including use in fragrances, cosmetics, insect repellents, and as a bioactive compound with antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, and anticancer effects with beneficial effects in neurological and cardiovascular diseases. Due to limitations in plant extraction and variability in yield, biotechnological approaches have emerged as sustainable alternatives for citronellol production. This review provides a comprehensive overview of citronellol biosynthesis, spanning natural plant pathways and engineered microbial systems. Key enzymes such as geraniol synthase, citral reductases, and short-chain dehydrogenases are discussed in the context of cytosolic and plastidic biosynthetic routes. Advances in metabolic engineering, including enzyme cascade design, have enabled microbial hosts like E. coli, S. cerevisiae, and Y. lipolytica to produce citronellol from renewable feedstocks. Biotransformation strategies using whole-cell systems and purified enzymes have further expanded the repertoire of citronellol derivatives, including rose oxide. Fermentation optimization, scale-up strategies, and innovative bioreactor designs—such as gas-phase and two-phase systems—are highlighted for their role in enhancing monoterpene yields and mitigating volatility-related challenges. Analytical tools including GC-MS, chiral HPLC, and molecular docking are reviewed for compound characterization and bioactivity prediction. Functional studies underscore citronellol’s therapeutic potential, supported by network pharmacology and in vivo models.