Microorganisms are an excellent source of natural products skeletons because of their capability to synthesize a plethora of small molecules with fascinating chemical structures and potent biological properties. In the pos genomic era, information concerning the biosynthesis of secondary metabolite has been gained together with the observation that the number of genes encoding biosynthetic enzymes in fungi outnumbers the known secondary metabolites synthesized by these microorganisms, indicating that only a subset of biosynthetic pathway genes is expressed under standard laboratory culture conditions. One strategy to unlocked these cryptic secondary metabolites is modify the fermentation parameters1.
Penicillum brasilianum is a remarkable microorganism with great potential for secondary metabolite production with several biosynthetic pathways2. Modification of culture medium composition by CuSO4 supplementation led to the induction of a secondary metabolite identified as the cyclodepsipeptide JBIR 113 and the detection of cyclodepsipeptides JBIR 114 and 115 described for the first time in this species3. Aiming to explore the chemical diversity of P. brasilianum, the microorganism was cultured in Czapeck supplemented with MnSO4 (1.0 g / L) under static condition at room temperature for 20 days. After that, the crude extracts were obtained (broth and mycelium). Crude extracts were chromatographed on silica gel column to afford six fractions. UHPLC-UV shows the MeOH fraction (Fig. 1) is rich in viridicatumtoxin and derivatives. Antimicrobial activity was evaluated against Criptococcus neoformans, Criptococcus gatti, Paracoccidioides brasiliensis, Candida glabrata, Candida parapisiloses, Candida albicans, Aspergillus fumigatus and Staphylococcus aureus. The viridicatumtoxin and derivatives fraction was found very active in the bioassays exhibiting MIC values shown on Table 1. As perspectives of the work, we intend to isolate and identify the viridicatumtoxin derivatives and evaluate their respective biological activities against mutants of Aspergillus fumigatus in order to verify the action of these compounds.