Fucoidan-active enzymes: Recent progress in their heterologous expression and future prospects for applications
摘要
Fucoidans, also referred to as fucose-containing polysaccharides (FCPs), are structurally diverse sulfated polysaccharides predominantly found in brown seaweeds and certain marine invertebrates. They are widely recognized for their broad therapeutic and industrial potential. The bioactivities of these FCPs are highly dependent on their molecular weight distribution, degree and pattern of sulfation, and backbone architecture, representing a broad spectrum of related structures that can be selectively modified through enzymatic pathways. This review consolidates recent progress on fucoidan-active enzymes, including fucosyltransferases, sulfotransferases, fucoidanases, sulfatases, and fucosidases, focusing on their catalytic roles in fucoidan biosynthesis and degradation, as well as strategies to overcome challenges in their recombinant expression. Current efforts in bacterial and yeast hosts are critically evaluated, highlighting metabolic engineering to enhance GDP-l-fucose supply through targeted gene deletions and improved NADPH regeneration, alongside expression optimization via codon engineering, promoter tuning, and solubility-enhancing fusion tags. Advances in strain engineering (e.g., Escherichia coli SHuffle, Origami B, and yeast systems), chaperone-assisted folding, and extracellular secretion are assessed for their impact on protein solubility, stability, and functional activity. Fucoidanases and fucosidases are discussed with respect to vector selection, culture conditions, and strategies to mitigate aggregation and inclusion body formation. By bridging enzymology with protein engineering, this review provides an integrated overview of promising methods and persistent bottlenecks in the production of active, fucoidan-modifying enzymes. Enzymatic approaches are highlighted as sustainable and selective tools for producing low-molecular-weight fucoidans and defined fucooligosaccharides, providing insights into future efforts in marine glycoengineering, bioprocessing, and the development of bioactive fucoidan derivatives.