Lipoxins (LXs) have attracted widespread attention as a class of anti-inflammatory lipid mediators that are produced endogenously by the organism. LXs are arachidonic acid (ARA) derivatives that include four different structures: lipoxin A4 (LXA4), lipoxin B4 (LXB4), and the aspirin-induced differential isomers 15-epi-LXA4 and 15-epi-LXB4. Because of their unique biological activity of reducing inflammation in the body, LXs have great potential for neuroprotection, anti-inflammatory treatment of COVID-19, and other related diseases. The synthesis of LXs in vivo is achieved through the action of lipoxygenase (LO). As a kind of important enzyme, LO plays a major role in the physiological processes of living organisms in mammals and functions in some bacteria and fungi. This suggests new options for the synthesis of LXs in vitro. Meanwhile, there are other chemical and biochemical methods to synthesize LXs. In this review, the recent progress on physiological activity and synthetic pathways of LXs is summarized, and new insights into the synthesis of LXs in vitro are provided.

Pure or highly concentrated ionic liquids (ILs, C_IL > 40% v/v) have been widely applied for the preparation of value-added products from polysaccharides by breaking their hydrogen bonds. Reducing the dosage of ILs would benefit the establishment of a greener process. However, the effect of low-concentration ILs on the pretreatment of polysaccharides, especially water-soluble recalcitrant polysaccharides, has not been fully investigated. In this study, aqueous [Bmim]Cl (1-butyl-3-methylimidazolium chloride) with different dilution ratios was applied to treat xanthan gum (XG) and assist XG hydrolysis. Structural characterization and hydrolysate analyses showed that 1% (v/v) [Bmim]Cl could effectively break intramolecular hydrogen bonds of XG through the binding of [Bmim]⁺ to XG side chains, disrupting the XG conformation. Such changes increased the accessibility of XG for chemical reagents. Moreover, [Bmim]Cl could significantly increase the content of hydroxyl and superoxide radicals (from H₂O₂) in the reaction system. These interactions strengthened the acidic oxidative hydrolysis of XG. Notably, a low concentration of [Bmim]Cl was proved to inhibit the Maillard browning of the acidic oxidative hydrolysis system, which also contributed to XG degradation. Under hydrolysis conditions of 0.4 M HCl, 0.75% (w/v) H₂O₂ and 1% (v/v) [Bmim]Cl for 4 days at 80 °C, XG could be hydrolyzed into a mixture with a high dextrose equivalent value of 29.16% containing 25 types of oligosaccharides. Meanwhile, the XG hydrolysates showed good antioxidant ability and elicitor activity against soybean cotyledon. Our work should be valuable for establishing a green and economic platform for valorizing water-soluble recalcitrant polysaccharides.

Directed evolution, enzyme design, and effective immobilization have been used to improve the catalytic activity. Dynamic polymers offer a promising platform to improve enzyme activity in aqueous solutions. Here, amphiphilic dynamers and lipase self-assemble into nanoparticles of 150- to 600-nanometer diameter, showing remarkable threefold enhancement in catalytic activity. In addition, they also demonstrated the ability to promote the reversible refolding of the partially or completely denatured lipase. The catalytic efficiency is completed with its more convenient handling of dynameric nanoparticles facilitating the efficient recovery and reuse of the enzyme with cost-effective uses. Molecular simulation studies revealed an in-depth understanding of how the dynamer action mechanism affects the conformational changes of lipase. The dynamer served as an effective hydrophobic support, facilitating the lid opening and substrate access to the catalytic triad, resulting in a substantial activation with an improved stability and recyclability of the lipase.

Water content is an important factor in lipase-catalyzed reactions in organic media but is frequently ignored in the study of lipases by molecular dynamics (MD) simulation. In this study, Candida antarctica lipase B, Candida rugosa lipase and Rhizopus chinensis lipase were used as research models to explore the mechanisms of lipase in micro-aqueous organic solvent (MAOS) media. MD simulations indicated that lipases in MAOS systems showed unique conformations distinguished from those seen in non-aqueous organic solvent systems. The position of water molecules aggregated on the protein surface in MAOS media is the major determinant of the unique conformations of lipases and particularly impacts the distribution of hydrophilic and hydrophobic amino acids on the lipase surface. Additionally, two maxima were observed in the water-lipase radial distribution function in MAOS systems, implying the formation of two water shells around lipase in these systems. The energy landscapes of lipases along solvent accessible areas of catalytic residues and the minimum energy path indicated the dynamic open states of lipases in MAOS systems differ from those in other solvent environments. This study confirmed the necessity of considering the influence of the microenvironment on MD simulations of lipase-catalyzed reactions in organic media.