An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.

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Towards the sustainable discovery and development of new antibiotics

Genome sequencing of Streptomyces, myxobacteria, and fungi showed that although each strain contains genes that encode the enzymes to synthesize a plethora of potential secondary metabolites, only a fraction are expressed during fermentation. Interest has therefore grown in the activation of these cryptic pathways. We review current progress on this topic, describing concepts for activating silent genes, utilization of “natural” mutant-type RNA polymerases and rare earth elements, and the applicability of ribosome engineering to myxobacteria and fungi, the microbial groups known as excellent searching sources, as well as actinomycetes, for secondary metabolites.

New strategies for drug discovery: Activation of silent or weakly expressed microbial gene clusters

Bacillus thuringiensis, a leading biorational pesticide in the parasporal cycle, is considered to be a valuable source of commercially effective biopesticide for various isolates and subspecies at the stationary stage of its growth cycle. Control of some species of insecticide between Lepidoptera, Diptera, and Coleoptera. Blends should have the lowest resemblance toxins and a variety of action mechanisms, as their activity is the highest. Cry protein is completely different from conventional chemical pesticides that have made Cry Protein a core component of advanced natural insect resistance and predatory patterns.

Bacillus thuringiensis and its pesticidal crystal proteins

The continued universal application of synthetic colorants for decades have caused environmental pollutions and human health vulnerabilities. So, it was indispensable to discover novel natural colorants such as microbial colorants which were safer and better than synthetic colorants. The potential of bacterial pigments for mass production of diversified coloring properties was first prospective and is now getting the notable importance and attention of both the researchers and industries. Literature establishes that the natural colorants produced from microbes were applied in food and pharma products successfully. Apart from serving as food colorants, bacterial pigments have several pharmacological activities like anti-microbial, anti-cancer, anti-oxidant, anti-inflammatory and anti-allergic properties with large economic potential. And, there is vast scope for easy and cheap production of natural colorants in all seasons from bacterial sources, compared to plant sources. Tactics in strain improvement, fermentation conditions, metabolic engineering, and easy extraction techniques are needed to produce high end products. This review highlights the significance of bacterial colorants and summarizes its application in food and pharma industries. Further, the major challenge of lower stability of bacterial pigments and the solution to address it is also appraised.

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Bacterial Pigments: Sustainable Compounds With Market Potential for Pharma and Food Industry

Natural products are used since ancient times in folklore for the treatment of various ailments. Plant-derived products have been recognized for many years as a source of therapeutic agents and structural diversity. A literature survey has been carried out to determine the utility of natural molecules and their modified analogs or derivatives as pharmacological active entities. This review presents a study on the importance of natural products in terms of drug discovery and development. It describes how the natural components can be utilized after small modifications in new perspectives. Various new modifications in structure offer a unique opportunity to establish a new molecular entity with better pharmacological potential. It was concluded that in this current era, new attempts are taken to utilize the compounds derived from natural sources as novel drug candidates, with a focus to find and discover new effective molecules that were referred to as "new entities of natural product drug discovery."

Natural products: A lead for drug discovery and development.

A variety of organisms, such as bacteria, fungi, and plants, produce secondary metabolites, also known as natural products. Natural products have been a prolific source and an inspiration for numerous medical agents with widely divergent chemical structures and biological activities, including antimicrobial, immunosuppressive, anticancer, and anti-inflammatory activities, many of which have been developed as treatments and have potential therapeutic applications for human diseases. Aside from natural products, the recent development of recombinant DNA technology has sparked the development of a wide array of biopharmaceutical products, such as recombinant proteins, offering significant advances in treating a broad spectrum of medical illnesses and conditions. Herein, we will introduce the structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control. In addition, we will explore past and ongoing efforts along with achievements in the development of robust and promising microorganisms as cell factories to produce biologically active molecules. Furthermore, we will review multi-disciplinary and comprehensive engineering approaches directed at improving yields of microbial production of natural products and proteins and generating novel molecules. Throughout this article, we will suggest ways in which microbial-derived biologically active molecular entities and their analogs could continue to inspire the development of new therapeutic agents in academia and industry.

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Murtadha T. Majid

Papers

A Review of the Microbial Production of Bioactive Natural Products and Biologics.