Impact of novel microbial secondary metabolites on the pharma industry

Abstract

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. Keywords Microbial natural products • Antibiotics • Hypocholesterolemics• Anticancer drugs • Immunosuppressants • Antibiotic resistance Abbreviations FDA Food and Drug Administration NA Not applicable cSSSI Complicated skin, and skin structure infections ABSSSIs Acute bacterial skin, and skin structure infections cUTI Complicated urinary tract infections cIAI Complicated intra-abdominal infections HABP/VABP Hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia CABP Community-acquired bacterial pneumonia. Estimate of U.S. Sales for 2018 was based on data previously reported Carr and Stringer 2019 * Sergio Sánchez

Identification of an ergosterol derivative with anti-melanoma effect from the sponge-derived fungus Pestalotiopsis sp. XWS03F09

“…In recent years, due to the wide sources of natural products, more and more studies have been conducted on their anti-tumor effects ( Fontana et al, 2019 ). Especially, microbial secondary metabolites have become a rich source of new drugs, which have made great contributions to the discovery of new drugs ( Lei et al, 2021 ; Ramirez-Rendon et al, 2022 ).…”

“…In the last few years, a growing interest in microbial secondary metabolites reflects the importance of microbial secondary metabolites in the discovery and development of new drugs which might be associated with their rich chemical structure ( Shen and Thorson, 2012 ; Wright, 2019 ; Maglangit et al, 2021 ). At present, a large number of natural products have been isolated from microbial secondary metabolites and have shown significant biological activities ( Yi et al, 2020 ; Ramirez-Rendon et al, 2022 ). Among them, marine microorganisms play a major role in the research of natural products, inhabiting environments with extremely high salinity, high pressure, low temperature, and low oxygen for a long time, resulting in a wide variety of secondary metabolites and novel structures.…”

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

“…Various microbially derived metabolites serve as ligands to xenobiotic nuclear receptors. Microbial metabolites with host protective properties (e.g., intestinal inflammation/obesity and short-chain fatty acids, indole metabolites), per se, have been proposed as sources for developing new drugs (Giddings and Newman 2013, Saha, Rajpal et al 2016, Stringlis, Zhang et al 2018, Descamps, Herrmann et al 2019, Raihan, Rabbee et al 2021, Ramírez-Rendon, Passari et al 2022). The use of purified microbial metabolites as drugs has had mixed results.…”

Natural products, including a new caboxamycin, from Streptomyces and other Actinobacteria isolated in Spain from storm clouds transported by Northern winds of Arctic origin

“…Members of the Phylum Actinobacteria, also known as actinomycetes, are major producers of secondary metabolites of medical and biotechnological use, being the Streptomyces genus the most prolific source of natural products of pharmaceutical interest. At present, there is an urgent need of new secondary metabolites, essentially antibiotics to combat pathogenic resistant bacteria, but also compounds with applications as anticancer agents, antivirals, antiparasitics and immunosuppresants, among others ( Ramirez-Rendon et al, 2022 ).…”