Expansion of natural library of bioactive microviridins of Brazilian cyanobacterial blooms through metagenomic mining approaches

Abstract

Cyanobacteria have been recently rediscovered as proficient producers of bioactive secondary metabolites, particularly polyketides, alkaloids and peptides. Noteworthy are the cyclic peptides as microviridins that form a new class of ribosomally synthesized depsipeptides, and whose intriguing tricyclic structure is unprecedented in nature. Due to their inhibitory activity against proteases, microviridins have a great potential for the treatment of diseases such as pulmonary emphysema, cystic fibrosis or infections. The family of cyanobacterial tricyclic peptides comprises thirteen variants, but data from environmental studies under the view of metagenomics suggest that the genetic diversity of microviridins is much larger than expected. In recent years metagenomics has been rapidly established as an efficient approach for discovery of new bioactive compounds independent of cultivation, which allows access to the genes of any sequence or function of a given environmental material. It offers modem techniques to characterize genes, biosynthetic gene clusters or even the metabolic profiles of complex samples, such as cyanobacteria blooms that hide an invaluable genetic variability, in many cases cryptic, for the production of bioactive secondary metabolites. Using a metagenomic mining approach to study a collection of environmental samples revealed a surprising variability of genes involved with the synthesis of microviridins expanding the natural library of these tricyclic peptides. Based on the use of the metagenomics approach applied to the chemical of natural products, this project aims the bioprospection of cryptic microviridins from Brazilian cyanobacterial blooms. Accessing the genetic heritage of this complex unknown biodiversity - quickly, efficiently and systematically - assumes a key position in the era of metagenomics and promises elegantly to unravel and expand the natural metabolomic library. (AU)