Integrated Enzymatic and Fermentative Pathways for Next-Generation Biosurfactants: Advances in Process Design, Functionalization, and Industrial Scale-Up

The global change toward sustainable manufacturing has intensified the development of alternatives to petrochemical-based surfactants, which are environmentally recalcitrant and fossil dependent. Biosurfactants have emerged as the most promising petrochemical-based surfactant substitutes, due to their biodegradability, low toxicity, and robust performance under extreme conditions; however, their industrial use is hindered by high production costs, limited productivity, and complex downstream processing, for instance high protein content can make the ultrafiltration (downstream strategy) unfeasible. This review critically examines recent advances in integrated bioprocess design to overcoming these constraints, with particular emphasis on the convergence of enzymatic catalysis and microbial fermentation. Comparative assessment across key biosurfactant classes demonstrates that tailored enzymatic transformations, enabled by lipases, glycosyltransferases, acyltransferases, and oxidoreductases, offer precision in structural modification unattainable through fermentation alone, enabling programmable amphiphilicity and improved functional performance. Thus, the translation of enzymatic and hybrid routes to industry remains restricted by enzyme stability, cofactor regeneration, and process engineering challenges. Emerging strategies such as continuous fermentation, in situ product recovery, and machine learning-based process control show strong potential to enhance productivity and reduce energy demands. By integrating molecular design, metabolic engineering, and intensified bioprocessing, this review delineates a strategic framework for advancing next-generation biosurfactants toward commercial viability within circular and sustainable value chains.