Metabolic diversification of Penicillium fungi isolated from the Atlantic Forest and Amazon biomes: a perspective for biomolecules production

Abstract

Penicillium genus represents one of the greatest sources of all known fungal chemodiversity. Currently, the genus is listed as the second main producer of known secondary metabolites among the ascomycetes. However, the occurrence of cryptic and/or silenced biosynthetic gene clusters in fungi suggests that most of the natural products potentially produced by Penicillium are still untapped. For example, after genome sequence from only twenty-four Penicillium species, more than a thousand putative biosynthetic gene clusters have been recently detected. Another important issue concerns the fact that most of the fungi species from global biodiversity hotspots, seem to be underexplored from the chemical point of view. This scenario represents a good opportunity for handling the secondary metabolism from those microorganisms, in order to find out biomolecules that could assist the development of likely therapeutic agents. In particular, molecules which could be applied for struggling the greatest challenges of public health nowadays: infectious diseases caused by multidrug-resistant bacteria and the cancers. Aiming to perform more suitable and effective strategy for accessing those molecules, the project combines genomic, chemical and biological approaches for prospecting the natural products produced by Penicillium species from Atlantic Forest and Amazonia. The identification of biosynthetic gene clusters and the corresponding secondary metabolites will be carried out trough genome mining of the target microorganisms. The presence of inactive gene clusters will be investigated when associated to the use of standard conditions for microbial growth at laboratory, guiding the detection of unknown bioactive compounds. In order to unveil and to provide the access to the chemical diversity of compounds produced by the target species, combined top-down approaches will be carried out to activate genes and unlocking biosynthetic pathways. The obtained molecular targets will be assessed for antimicrobial activity against multidrug resistant bacteria as well as for their cytotoxicity in human leukemia cell lines. In addition to the discovery and the characterization of new natural products, this project could assist the preliminary outlines and understandings of biosynthetic pathways corresponding to still unexplored fungal biomolecules. (AU)