Biosynthetic studies involving bottom-up approaches of polyketides produced by Penicillium species

Abstract

Biosynthesis of microbial natural products has aroused great interest in the scientific community and genetic studies of microorganisms already seem to represent the reality of modern research involving microbial biosynthesis of natural products. The fungus Penicillium brasilianum recently had its genome sequenced and the final assembly revealed 252 supercontigs which underwent gene predictions and automatic annotation. Functional genome analysis revealed 69 possible biosynthetic clusters, 11 clusters related to the biosynthesis of polyketides via PKS enzymes (polyketides synthase); 12 different clusters involved in the production of secondary metabolites formed via NRPS enzymes (non-ribosomal peptide synthetases) and 6 hybrids biosynthetic clusters, including the hybrid terpene-NRPS responsible for biosynthesis of alkaloids, indicating the great potential of this organism to produce bioactive secondary metabolites. The fungus Penicillium digitatum also is an interesting target for biosynthetic studies, mainly due to their pathogenicity against citrus, a serious problem for agriculture. Studies of their secondary metabolism and their respective biosynthesis would contribute greatly to the country. The fungus P. digitatum was recently sequenced and analysis of biosynthetic clusters of P. digitatum indicated 24 possible clusters, including 13 involved in the biosynthesis of peptides (NRPS enzymes), 14 possible clusters involved in the biosynthesis of polyketides via PKS enzymes and 3 clusters encoding the production of hybrid NRPS/PKS metabolites, indicating the potential of the targeted microorganisms. Thus, the project aims molecular biology studies and genetic studies of such fungi in the Organic Chemistry Department at the Chemistry Institute of UNICAMP, which converge to the possibility of biosynthetic studies of gene clusters of natural products found in Penicillium species, as well as enzyme studies using heterologous expression of biosynthetic enzymes of interest. (AU)