A strategy for the identification of patterns in the biosynthesis of nonribosomal peptides by Betaproteobacteria species.

Nonribosomal peptides have an important pharmacological role due to their extensive biological properties. The singularities in the biosynthesis of these natural products allowed the development of genome-mining strategies which associate them to their original biosynthetic gene clusters. Generally, these compounds present complex architectures that make their identification difficult. Based on these evidences, genomes from species of the class Betaproteobacteria were studied with the purpose of finding biosynthetic similarities among them. These organisms were applied as templates due to their large number of biosynthetic gene clusters and the natural products isolated from them. The strategy for Rapid Identification of Nonribosomal Peptides Portions (RINPEP) proposed in this work was built by reorganizing the data obtained from antiSMASH and NCBI with a product-centered way. The verification steps of RINPEP comprehended the fragments of existent compounds and predictions obtained in silico with the purpose of finding common subunits expressed by different genomic sequences. The results of this strategy revealed patterns in a global overview of the biosynthesis of nonribosomal peptides by Betaproteobacteria.

The Correlation between Chemical Structures and Antioxidant, Prooxidant, and Antitrypanosomatid Properties of Flavonoids.

Flavonoids have demonstrated in vivo and in vitro leishmanicidal, trypanocidal, antioxidant, and prooxidant properties. The chemotherapy of trypanosomiasis and leishmaniasis lacks efficacy, presents high toxicity, and is related to the development of drug resistance. Thus, a series of 40 flavonoids were investigated with the purpose of correlating these properties via structure and activity analyses based on integrated networks and QSAR models. The classical groups for the antioxidant activity of flavonoids were combined in order to explain the influence of antioxidant and prooxidant activities on the antiparasitic properties. These analyses become useful for the development of efficient treatments for leishmaniasis and trypanosomiasis. Finally, the dual activity of flavonoids presenting both anti- and prooxidant activities revealed that the existence of a balance between these two features could be important to the development of adequate therapeutic strategies.