Bioprospection in fungi: the search of lead compounds for drug design and enzymes for pharmaceutical and industrial applications

Abstract

Fungi have been less explored than plants in bioprospection programs, especially the endophytes, which remain a promising and practically unexplored source of interesting bioactive natural products. One of the major advantages of working with microorganisms in a natural products discovery program is the possibility to screen a vast number of cultures on a small scale, before identifying the microorganisms, while retaining a high probability of success in reproducing both the activity and the metabolite production on a large-scale fermentation. Another advantage is that manipulations in culture conditions may lead to a wider range of compounds produced by fungi than it would be available from traditional production of extracts from plants. In this project we propose to exploit the chemical and biological potential of endophytic and soil fungi collected in São Paulo State in three approaches: i) obtainment of crude extracts from microbial cultures to be evaluated in antimicrobial assays performed in our labs and other bioassays provided by the network. The most promising extracts will be fractionated, aiming to obtain new leads for drug development; ii) obtainment of products from biotransformation reactions of bioactive natural products previously isolated in our labs (grandisin, budlein A and tagitinin C) and evaluation of their biological activities in bioassays of the network, and iii) production of enzymes, which might be useful in industrial processes (xylanase, glucose oxidase, phytase, amylase, acid and alkaline phosphatases) and as new pharmaceuticals (L-asparaginase). The proposed antimicrobial screening, as the first one, may be an indication of a wider ranger of bioactivity which shall be detected by the other assays available in the network. (AU)