Nonribosomal peptides are products that fall into the class of secondary metabolites with a diverse properties as toxins, siderophores, pigments, or antibiotics, among others. Unlike other proteins, its biosynthesis is independent of ribosomal machinery. Nonribosomal peptides are synthesized on large nonribosomal peptide synthetase (NRPS) enzyme complexes. NRPSs are defined as multimodular enzymes, consisting of repeated modules. The NRPS enzymes are at operons and their regulation can be positive or negative at transcriptional or post-translational level. The presence of NRPS enzymes has been reported in the three domains of life, being prevalent in bacteria. Nonribosomal peptides are use in human medicine, crop protection, or environment restoration; and their use as commercial products has been approved by the U. S Food and Drug Administration (FDA) and the U. S. Environmental Protection Agency (EPA). The key features of nonribosomal peptides and NRPS enzymes, and some of their applications in industry are summarized.

Gene regulation at the transcriptional level is a central process in all organisms, and DNA-binding transcription factors, known as TFs, play a fundamental role. This class of proteins usually binds at specific DNA sequences, activating or repressing gene expression. In general, TFs are composed of two domains: the DNA-binding domain (DBD) and an extra domain, which in this work we have named “companion domain” (CD). This latter could be involved in one or more functions such as ligand binding, protein-protein interactions or even with enzymatic activity. In contrast to DBDs, which have been widely characterized both experimentally and bioinformatically, information on the abundance, distribution, variability and possible role of the CDs is scarce. Here, we investigated these issues associated with the domain architectures of TFs in prokaryotic genomes. To this end, 19 families of TFs in 761 non-redundant bacterial and archaeal genomes were evaluated. In this regard we found four main groups based on the abundance and distribution in the analyzed genomes: i) LysR and TetR/AcrR; ii) AraC/XylS, SinR, and others; iii) Lrp, Fis, ArsR, and others; and iv) a group that included only two families, ArgR and BirA. Based on a classification of the organisms according to the life-styles, a major abundance of regulatory families in free-living organisms, in contrast with pathogenic, extremophilic or intracellular organisms, was identified. Finally, the protein architecture diversity associated to the 19 families considering a weight score for domain promiscuity evidenced which regulatory families were characterized by either a large diversity of CDs, here named as “promiscuous” families given the elevated number of variable domains found in those TFs, or a low diversity of CDs. Altogether this information helped us to understand the diversity and distribution of the 19 Prokaryotes TF families. Moreover, initial steps were taken to comprehend the variability of the extra domain in those TFs, which eventually might assist in evolutionary and functional studies.

The Pelibuey sheep has adaptability to climatic variations, resistance to parasites, and good maternal ability, whereas some ewes present multiple births, which increases the litter size in farm sheep. The litter size in some wool sheep breeds is associated with the presence of mutations, mainly in the family of the transforming growth factor β (TGF-β) genes. To explore genetic mechanisms underlying the variation in litter size, we conducted a genome-wide association study in two groups of Pelibuey sheep (multiparous sheep with two lambs per birth vs. uniparous sheep with a single lamb at birth) using the OvineSNP50 BeadChip. We identified a total of 57 putative SNPs markers (p < 3.0 × 10⁻³, Bonferroni correction). The candidate genes that may be associated with litter size in Pelibuey sheep are CLSTN2, MTMR2, DLG1, CGA, ABCG5, TRPM6, and HTR1E. Genomic regions were also identified that contain three quantitative trait loci (QTLs) for aseasonal reproduction (ASREP), milk yield (MY), and body weight (BW). These results allowed us to identify SNPs associated with genes that could be involved in the reproductive process related to prolificacy.

Background: The regulation of gene expression at the transcriptional level is a fundamental process in prokaryotes. Among the different kind of mechanisms modulating gene transcription, the one based on DNA binding transcription factors, is the most extensively studied and the results, for a great number of model organisms, have been compiled making it possible the in silico construction of their corresponding transcriptional regulatory networks and the analysis of the biological relationships of the components of these intricate networks, that allows to elucidate the significant aspects of their organization and evolution. Results: We present a thorough review of each regulatory element that constitutes the transcriptional regulatory network of Bacillus subtilis. For facilitating the discussion, we organized the network in topological modules. Our study highlight the importance of σ factors, some of them acting as master regulators which characterize modules by inter- or intra-connecting them and play a key role in the cascades that define relevant cellular processes in this organism. We discussed that some particular functions were distributed in more than one module and that some modules contained more than one related function. We confirm that the presence of paralogous proteins confers advantages to B. subtilis to adapt and select strategies to successfully face the extreme and changing environmental conditions in which it lives. Conclusions: The intricate organization is the product of a non-random network evolution that primarily follows a hierarchical organization based on the presence of transcription and σ factor, which is reflected in the connections that exist within and between modules.

Extensive genomic studies on gene duplication in model organisms such as Escherichia coli and Saccharomyces cerevisiae have recently been undertaken. In these models, it is commonly considered that a duplication event may include a transcription factor (TF), a target gene, or both. Following a gene duplication episode, varying scenarios have been postulated to describe the evolution of the regulatory network. However, in most of these, the TFs have emerged as the most important and in some cases the only factor shaping the regulatory network as the organism responds to a natural selection process, in order to fulfil its metabolic needs. Recent findings concerning the regulatory role played by elements other than TFs have indicated the need to reassess these early models. Thus, we performed an exhaustive review of paralogous gene regulation in E. coli and Bacillus subtilis based on published information, available in the NCBI PubMed database and in well-established regulatory databases. Our survey reinforces the notion that despite TFs being the most prominent components shaping the regulatory networks, other elements are also important. These include small RNAs, riboswitches, RNA-binding proteins, sigma factors, protein–protein interactions and DNA supercoiling, which modulate the expression of genes involved in particular metabolic processes or induce a more complex response in terms of the regulatory networks of paralogous genes in an integrated interplay with TFs.

The ability of bacteria and archaea to modulate metabolic process, defensive response, and pathogenic capabilities depend on their repertoire of genes and capacity to regulate the expression of them. Transcription factors (TFs) have fundamental roles in controlling these processes. TFs are proteins dedicated to favor and/or impede the activity of the RNA polymerase. In prokaryotes these proteins have been grouped into families that can be found in most of the different taxonomic divisions. In this work, the association between the expansion patterns of 111 protein regulatory families was systematically evaluated in 1351 non-redundant prokaryotic genomes. This analysis provides insights into the functional and evolutionary constraints imposed on different classes of regulatory factors in bacterial and archaeal organisms. Based on their distribution, we found a relationship between the contents of some TF families and genome size. For example, nine TF families that represent 43.7% of the complete collection of TFs are closely associated with genome size; i.e., in large genomes, members of these families are also abundant, but when a genome is small, such TF family sizes are decreased. In contrast, almost 102 families (56.3% of the collection) do not exhibit or show only a low correlation with the genome size, suggesting that a large proportion of duplication or gene loss events occur independently of the genome size and that various yet-unexplored questions about the evolution of these TF families remain. In addition, we identified a group of families that have a similar distribution pattern across Bacteria and Archaea, suggesting common functional and probable coevolution processes, and a group of families universally distributed among all the genomes. Finally, a specific association between the TF families and their additional domains was identified, suggesting that the families sense specific signals or make specific protein-protein contacts to achieve the regulatory roles.