Abstract Description

Lanthipeptides are post-translationally modified peptides produced by a wide variety of Gram-positive bacteria and, to a lesser extent, by certain Gram-negative species. Among them, lantibiotics represent a well-studied subclass with broad biological activities, including antibacterial, antiviral, immunomodulatory, and antifungal effects. Their biosynthetic gene clusters encode all the essential components for peptide maturation, export, regulation, and self-immunity, typically involving lanA (structural), lanB/lanC (or lanM) (modification), lanT (transporter), lanR/lanK (regulators), and lanI/lanEFG (immunity proteins) genes. The opportunistic fungal pathogen Candida albicans remains a major clinical challenge due to its ability to form biofilms and its increasing resistance to existing antifungal drugs such as azoles and amphotericin B, which are often limited by host toxicity. This underscores the need for novel and safer antifungal agents with new mechanisms of action. This study aimed to investigate the antifungal potential of the lantibiotic pinensin and a novel lantibiotic, japonensin, identified through genome mining and naturally produced by the Gram-negative bacteria Chitinophaga pinensis and Chitinophaga japonensis. Fermentations (3 L scale) were performed for each strain under controlled bioreactor conditions, and the target compounds were purified from culture supernatants using hydrophobic interaction techniques, including XAD-resin adsorption and C18 reversed-phase chromatography. The purified peptides were subsequently evaluated for antimicrobial activity using agar diffusion and minimum inhibitory concentration assays. Preliminary bioassays demonstrated clear inhibitory activity against the indicator strain Lactobacillus sakei, confirming bioactive peptide production. Ongoing work aims to evaluate antifungal efficacy against clinically relevant Candida albicans derivatives. These findings confirm the production of bioactive lantibiotics by Gram-negative Chitinophaga species and provide a foundation for evaluating the antifungal potential of pinensin and japonensin. Given the genetic accessibility of lantibiotic biosynthetic clusters and the feasibility of heterologous expression in E. coli for enhanced production, pinensin and japonensin hold promise as future antifungal candidates with novel mechanisms of action and potentially reduced toxicity.