Advances in microbial mevalonolactone production: from fermentative mevalonate accumulation to downstream lactonization

Mevalonolactone (MVAL) is a high-value feedstock for the cosmetic industry, with ( R )-(-)-MVAL as the sole bioactive enantiomer. Chemical synthesis, which is the traditional method for MVAL production, is hindered by cumbersome procedures, low chiral purity, and sensitivity to humidity. Microbial fermentation via fermentative mevalonate (MVA) accumulation followed by in vitro acid-catalyzed lactonization has emerged as a promising alternative for producing optically pure ( R )-(-)-MVAL. Strategies for MVA overproduction in microbial systems are reviewed, including the selection of chassis strains and enzymes for the MVA biosynthetic pathway, metabolic engineering approaches for strain improvement, optimization of fermentation processes, and downstream processes for MVA-to-MVAL lactonization. Finally, prospects for advancing microbial MVAL production are discussed.