Introduction: The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts. Areas covered: The low yield and the therefore difficult extraction and purification process in AMPs are problems that limit their industrial application and scientific research. Thus, optimized heterologous expression systems were developed to significantly boost AMP yields, allow high efficiency in purification and structural optimization for the increase of therapeutic activity. Expert opinion: This review provides an update on recent developments in the recombinant production of ribosomal and non-ribosomal synthesis of AMPs and on strategies to increase the expression of genes encoding AMPs at the transcriptional and translational levels and regulation of the post-translational modifications. Moreover, there are detailed reports of AMPs that have already reached marketable status or are in the pipeline under advanced stages of preclinical testing.
The extensive use of antibiotics during recent years has led to antimicrobial resistance development, a significant threat to global public health. It is estimated that around 1.27 million people died worldwide in 2019 due to infectious diseases caused by antibiotic-resistant microorganisms, according to the WHO. It is estimated that 700,000 people die each year worldwide, which is expected to rise to 10 million by 2050. Therefore, new and efficient antimicrobials against resistant pathogenic bacteria are urgently needed. Antimicrobial peptides (AMPs) present a broad spectrum of antibacterial effects and are considered potential tools for developing novel therapies to combat resistant infections. However, their clinical application is currently limited due to instability, low selectivity, toxicity, and limited bioavailability, resulting in a narrow therapeutic window. Here we describe an overview of the clinical application of AMPs against resistant bacterial infections through nanoformulation. It evaluates metal, polymeric, and lipid AMP delivery systems as promising for the treatment of resistant bacterial infections, offering a potential solution to the aforementioned limitations.
N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide’s secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu2+, Ni2+, and Zn2+, give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials.
Genome editing technologies have revolutionized the production of microorganisms, plants, and animals with phenotypes of interest to agriculture. Editing previously sequenced genomes allows for the punctual, discreet, precise, and accurate alteration of DNA for genetic analysis, genotyping, and phenotyping, as well as the production of edited organisms for academic and industrial purposes, among many other objectives. In this context, genome editing technologies have been causing a revolution in Brazilian agriculture. Thanks to the publication of Normative Resolution No. 16 (in Portuguese Resolução Normativa No. 16-RN16) in 2018, Brazilian regulatory authorities have adapted to the new genetic manipulation technologies available to the scientific community. This review aims to describe the effects of updates to the regulatory framework for edited organisms in Brazil and to point out their impacts on research and development of emerging technologies in the Brazilian agricultural sector. The implementation of RN16 rationalized the regulatory aspects regarding the production, manipulation, exploration and commercial release of edited organisms and led to the faster, cheaper and safer obtaining of edited technologies, which are more productive and better adapted to different environmental conditions in Brazil.