RESUMO

Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs. Since then, antibiotics have played a valuable role in treating infectious diseases and have saved many human lives. New molecules with anticancer, hypocholesterolemic, and immunosuppressive activity have now been introduced to treat other relevant diseases. Smaller biotechnology companies and academic laboratories generate novel antibiotics and other secondary metabolites that big pharmaceutical companies no longer develop. The purpose of this review is to illustrate some of the recent developments and to show the potential that some modern technologies like metagenomics and genome mining offer for the discovery and development of new molecules, with different functions like therapeutic alternatives needed to overcome current severe problems, such as the SARS-CoV-2 pandemic, antibiotic resistance, and other emerging diseases. KEY POINTS: • Novel alternatives for the treatment of infections caused by bacteria, fungi, and viruses. • Second wave of efforts of microbial origin against SARS-CoV-2 and related variants. • Microbial drugs used in clinical practice as hypocholesterolemic agents, immunosuppressants, and anticancer therapy.

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RESUMO

In recent years, the number of pathogenic microorganisms resistant to antibiotics has increased alarmingly. For the next 10-20 years, health organizations forecast high human mortality caused by these microorganisms. Therefore, the search for new anti-infectives is quite necessary and urgent. Traditionally, antibiotic-producing microorganisms have been isolated from common soil samples. However, this source seems to be exhausted considering the very few examples of antibiotic-producing microorganisms reported recently. In this review, non-conventional sources of anti-infective producing microorganisms are presented as a possible way to look for new and more effective compounds. These sources included arid soils, caves, areas with high temperatures (hot springs), high salinity or oceans and seas. Finally, other non-conventional sources of antibiotics reviewed are animal and invertebrate venoms, among others.

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Fermentative production of amino acids is an important goal of modern biotechnology. Through fermentation, micro-organisms growing on inexpensive carbon and nitrogen sources can produce a wide array of valuable products including amino acids. The amino acid market is $8 billion and mainly impacts the food, pharmaceutical and cosmetics industries. In terms of tons of amino acids produced per year by fermentation, L-glutamate is the most important amino acid produced (3.3 million), followed by L-lysine (2.2 million). The bacteria producing these amino acids are among the top fermentation organisms with respect to titers. Corynebacterium glutamicum is the best producer.The Journal of Antibiotics advance online publication, 1 November 2017; doi:10.1038/ja.2017.142.

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RESUMO

Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalysing metabolic reactions in microbial cells is controlled by well-known positive and negative mechanisms, e.g. induction, nutritional regulation (carbon or nitrogen source regulation), feedback regulation, etc. The microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids and vitamins which can be added to food to enhance its flavour, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum-derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on. In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome and metabolome analysis, as well as metabolic flux analysis. have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement.

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