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4INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
RECENT ADVANCEMENTS IN MICROBIOLOGICAL APPROACHES TO DRUG DISCOVERY
1Pushpendra Soni, 2Dr. Shorn Prakash Kushwaha, 3Dr. (Prof.) Syed Misbahul Hasan, 4Dr.
Kuldeep Singh, 5Dr. Arun Kumar, 6Riya Yadav
1Student, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow, Uttar
Pradesh, India
2Associate Professor, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow,
Uttar Pradesh, India
3Dean & Professor, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow,
Uttar Pradesh, India
4Professor, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow, Uttar
Pradesh, India
5Associate Professor, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow,
Uttar Pradesh, India
6Student, Faculty of Pharmacy, Integral University, Dasauli, Kursi Road, Lucknow, Uttar
Pradesh, India https://doi.org/10.5281/zenodo.13846807
Abstract. The process of identifying new therapeutic agents can be considered the key to improving medical treatment and preventing new diseases. Conventional drug discovery relies mostly on chemical synthesis powered by guesswork and trial-and-error approaches, but with the application of microbiology, the situation changes drastically with the use of bacteria, fungi, and actinomycetes. These microbes synthesize an impressive number of bioactive metabolites that yield remarkable biological activities, such as antibacterial, antitumor, and immunomodulatory properties, that propound them for use as drugs. Microbiological techniques are slowly taking center stage in the drug discovery process because of developments that have occurred in the recent past. High-throughput screening (HTS) facilitates the assessment of many microbial and chemical cocktails and expedites the discovery of new drugs. Metagenomics improves this process because it involves sequencing samples of genetic material extracted from the environment and identifying new biosynthetic pathways and products derivedfrom previously unstudied microbial populations. Genomic information is used to understand the genetic regulation of secondary metabolites and thus to increase or engineer microbes to produce further bioactive molecules. In addition, new interdisciplinary fields, such as synthetic biology and microbial engineering, have brought about new solutions for formulating and constructing new biosynthetic pathways and synthesizing high-value natural herb products. These techniques have led to the discovery of new antibiotics and anticancer compounds.
Introduction
More recently, however, microbiology has become very important in the biological discovery of new entities through their use of microorganisms and their bioactivity. Microbes, particularly bacterial fungi and actinomycetes, are known to biosynthesize several natural products, many possess diverse biological activities, such as antimicrobial, anticancer, and immunomodulatory effects, making them candidates for drug molecules.[1] Nevertheless, the outcomes have been impressive; recent developments in various microbiological methods, such as
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
high-throughput screening methods and metagenome biochemistry, have greatly increased the number of drug discoveries. Drug discovery has advanced in microbial engineering as well as synthetic biology because it makes it possible for new molecules to be produced or the biological activity of known bioactive compounds to be increased. [2] However, there are currently several issues, such as the growth of new microbes, the ability to work with natural product chemical structures, and their incorporation in drug discovery.
Microbiological Techniques in Drug Discovery
Microbiology plays an important role in drug discovery, as some of the most effective therapeutic technologies involve these methods. High-throughput screening or HTS is possibly one of the most influential among all the known techniques. HTS can help researchers quickly access large databases of microbial samples or chemical compounds for bioactivity. Compared with conventional drug discovery methods, HTS enables the analysis of large numbers of microbial extracts or synthetic compounds so that the drug discovery process is accelerated and the chances of discovering new therapeutic agents with favorable pharmacokinetic profiles are increased.[3]
Another major development is metagenomics, where the genomes of samples obtained from the environment are sequenced without the need to culture microbes in the laboratory. Metagenomics provides an overview of microbial community composition and defines novel biosynthetic pathways and natural products. According to the notion of metagenomics, researchers have found new compounds useful for treating diseases by analyzing the sum of all genes of microbial populations.[4]
Microbial genomics adds to the drug discovery process in two more ways: the detailed information emerging from genomics about the genetic basis of microbial secondary metabolism. Microbial genomics allows scientists to examine genes that create bioactive compounds by sequencing and analysis.[5]
Furthermore, with the help of microbial engineering and synthetic biology, new opportunities for the development of drugs have appeared. In this way, engineers can add new genes or change the existing genes in microbial genomes to develop a new biosynthetic method or to optimize an existing gene that synthesizes new chemical compounds.[6]
Innovative Microbial Sources for Drug Discovery
The search for novel sources of production has now extended into the unchartered frontiers of microorganisms, enriching the search for novel bioactive molecules.
New Microorganisms and Their Uses
New microbial strains are specifically targeted for screening, as various unexplored bioactive metabolites can be produced from novel microbial strains.Chemosynthetic niches are populated with microorganisms that possess unique metabolic profiles and biosynthetic processes, thus giving rise to novel chemical scaffolds and bioactive compounds.[7]
Synthetic Biology and Microbial Engineering
The inventions of synthetic biology and microbial engineering as fields have led to dramatic changes in drug discovery. By cultivating the microbial genome via synthetic biology, one can either increase the yield of known bioactive compounds or program the microbe to synthesize novel molecules. For example, synthetic biology has been applied to enhance the biosynthetic routes of famous antibiotics, such as penicillin and streptomycin, with better yields resulting in greater biological activity. [8]
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
Microbial engineering is also an important aspect of the drug discovery process. Scientists can change the composition of microorganisms to produce compounds that are not usually associated with microbes. This approach is well applicable in the manufacturing of costly natural products, such as the anticancer drug paclitaxel, which is derived from the Pacific yew tree but is currently synthesized via engineered microbial systems.[9]
Natural compounds are characterized via mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, and the biological activities of these compounds are evaluated. The discovery of natural products has provided a means of identifying many drugs, such as antibiotics such as vancomycin, and anticancer agents such as doxorubicin.[10]
Conclusion
The discovery of novel microbial targets has radically transformed the drug discovery process and introduced many bioactive compounds with considerable therapeutic value. The application of sophisticated methods of microorganism analysis, including high-throughput screening, metagenomic identification, and synthetic microbiology, has led to the discovery of new drugs.
The identification of new microbial strains that naturally populate extreme environments and the application of microbial engineering to select strains of interest has broadened the new drug lead spectrum even further. These developments demonstrate that microbiological methods remain valuable for drug discovery to address existing therapeutic gaps as well as existing limitations.
Figure: 1- Drug discovery using microbiology
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INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
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