Antifungal Activity and the Potential Correlation with Statin-Producing Ability: An Optimized Screening Applied to Filamentous Fungi from Las Yungas Subtropical Rainforest

摘要

Research was aimed at investigating statin-related antifungal activity of fungal specimens isolated from Las Yungas Pedemontana Forest. Considering the participation of statins as a potential mechanism for competition in natural environments, their production was particularly analyzed. Following the 'dereplication' concept for identifying natural products, extracts from fungal isolates were screened by yeast-growth inhibition bioassays, TLC and RP-HPLC analysis. Extraction from fungal cultures was performed according to three alternative protocols: glass-beads, Waring blender disruption, or a freeze-thawing method. Waring-blender-obtained fungal extracts led to higher yields of potentially statin-related compounds than those of glass-beads disruption or freeze-thawing. Around a 10% of 201 Las Yungas isolates showed statin-compatible TLC(+) profiles, thus being pre-selected as potential statin-producers. During yeast bioassays, 13 extracts inhibited S. cerevisiae ATCC 32051 growth whilst seven had the same effect on Candida utilis Pr_1-2. Some peaks revealed by RP-HPLC corresponded to known statins like pravastatin, lovastatin and simvastatin. Statin-producing isolates were identified as Hypocrea and Penicillium genera members. Despite the low statin titres (~3 mg L~-1), likely related to non-optimal production conditions, some fungal extracts were able to inhibit HMGCoA-reductase between 1.3 and 18.6%. Antifungal activities of selected isolates could be thus related to statin production, probably as a competition skill in natural ecosystems. This report highlights the hidden biotechnological potential, such as statin production ability, of indigenous filamentous fungi from subtropical rainforests of Las Yungas. Additionally, optimized protocols for statin-production assessment are herein proposed for future screening programs.