Enzymatic synthesis and biological evaluation of glycolipids as potential antibacterial, antibiofilm and antiquorum sensing agents

Abstract

Glycolipids are becoming an important class of biosurfactants with relevant antibacterial and antibiofilm properties. In this study, the enzymatic synthesis of glycolipids is reported, achieved through the regioselective transesterification of different sugars (fucose, arabinose, fructose, glucose, mannose, galactose, N-acetylglucosamine, N-acetylgalactosamine and maltose) with vinyl laurate. The biocatalyst employed for this process is the lipase from Pseudomonas stutzeri. The biocatalytic reaction proved to be very effective for the regioselective synthesis of lauroyl monoesters and diesters. Docking and molecular dynamic simulations studies were employed to explain enzyme's regioselectivity and its ability to accommodate sugar head, providing insights into the observed behavior. The antibacterial, antibiofilm and anti-quorum sensing activities of the synthesized glycolipids were evaluated against a target panel of Gram-positive and Gram-negative bacteria. While 6-O-lauroyl-Man (6) and 4-O-lauroyl-Rha (1e) exhibited the highest antibacterial activity in the monoester series, lauroyl diesters (4, 1,6-O-dilauroyl-Fru and 7, 2,6-O-dilauroyl-Gal) demonstrated increased activity compared to monoesters and displayed greater promise than the positive control. Regarding antibiofilm properties, 4-O-lauroyl-Rha (1e), 1,6-O-dilauroyl-Fru (4) and 2,6-O-dilauroyl-Gal (7) presented higher activity than the positive control on Gram-positive bacteria. Compounds 6-O-lauroyl-Man (6), 6-O-lauroyl-GlcNAc (8) and 6-O-lauroyl-GalNAc (9) showed high antibiofilm and anti-quorum sensing activities on Gram-negative bacteria, surpassing even the positive control. Docking studies provided a comprehensive understanding of the mechanisms behind their efficacy. In conclusions, a sustainable strategy has been performed to prepare glycolipids, offering promising prospects as antibacterial, antibiofilm and anti-quorum sensing agents. These glycolipids could serve as a viable alternative to conventional antibiotics in the future.