δ-Lactam from soil's fungus Humicola grisea var. thermoidea

Fungal secondary metabolites are extremely important to our health and nutrition, and have tremendous economic impact in our society. In addition to the multiple reaction sequences of fermentations, fungi are useful in carrying out biotransformation processes. These are becoming essential for the fine-chemical industry in the production of single-isomer intermediates. Fungal metabolites are used as antitumor, immunosuppressive, hypocholesterolemic, enzyme inhibitors, antimigraine, and antiparasitic agents. A number of these products was first discovered as antibiotics which failed in their development as such, or as mycotoxins [1]. The aim of this work was to evaluate the antimicrobial activity and applications of secondary metabolites produced by Humicola grisea var thermoidea. The production of secondary metabolites was carried out by cultivating 10⁶ spores/g in solid medium (rice) at 40°C for 60 days. The culture was harvested and submitted to the process of liquid-liquid partition with organic solvents. Then, the dichloromethanic extract was concentrated under vacuum, and submitted to vacuum liquid chromatography technique, followed by preparative thin layer chromatography and flash chromatography for the isolation of δ-lactam, which was elucidated by spectroscopy means (NMR). This compound was submitted to antibacterial assay to determine the minimum inhibitory concentrations (MIC) against Escherichia coli, Kocuria rhizophila, Pseudomonas aeruginosa and Staphylococcus aureus. The interval of concentrations evaluated was from 50µg/mL to 400µg/mL. The obtained MIC values against K. rhizophila and E. coli were 350 and 300µg/mL, respectively. Theδ-lactam was previously isolated from an algae-infested Caribean sponge, Halichondria melandocia. Therefore, it is the first time that this compound has been isolated from a fungus culture.

Acknowledgements: FAPESP

References: 1. Demain, A., Adrio, J. L. (2003) Int. Microbiol. 6:191–199.