Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.

1. DRUG DISCOVERY FROM
MICROBIAL GENOMES
by Lunjapikai Haokip, 2023395410
M. Sc Microbiology II Semester, Sharda University
Faculty In-charge: Dr. Subhabrata Kar.

2. CONTENTS
Introduction.
Success stories
Genomics
 HOW ARE DRUGS DISCOVERED
AND DEVELOPED?.
The Future of Microbial Drug
Discovery: Excitement and
Challenges
 Limitations
Conclusion.

3. INTRODUCTION
 Drug discovery from microbial genomes is crucial
for developing new medicines.
 Microorganisms produce a vast array of secondary
metabolites with potential therapeutic properties.
 These metabolites can serve as the basis for novel
drugs to treat various diseases, including
infections, cancer and neurological disorders.

4. Success Stories: Drugs Derived from
Microbes
 Penicillin: The first and most
influential antibiotic.
 Streptomycin: A key weapon
against tuberculosis.
 Artemisinin: A powerful anti-
malarial drug
 And many more!

5. Genomics: Unlocking the Secrets of Microbial Genomes
Whole-genome sequencing: Deciphering the genetic code
Bioinformatics tools: Mining for hidden gems and drug targets
Metagenomics: Exploring uncultured microbial communities

6.  Whole-genome sequencing (WGS) is a powerful technique that
involves reading and decoding the entire genetic information
(genome) of an organism.
 It provides insights into an individual’s unique genetic makeup,
including variations, mutations, and potential disease risk.
 By analyzing the complete DNA sequence, researchers can
identify genetic variations associated with diseases, drug
responses, and inherited conditions.
Whole-Genome Sequencing:

7. Mining for Hidden Gems and Drug Targets:
Bioinformatics tools help researchers sift through vast amounts of
genomic, proteomic, and metabolomic data. They identify potential drug
targets, predict protein structures, and analyze gene expression patterns.
These tools play a crucial role in drug discovery by identifying
candidate molecules that could be developed into effective therapies.

8. Metagenomics
– Metagenomics explores microbial communities without the need for
culturing individual organisms.
– Uncultured Microbial Communities: Most microbes in natural
environments cannot be grown in the lab. Metagenomics allows us to study
these uncultured microbes directly from environmental samples (such as
soil, water, or the human gut).
– By analyzing their DNA, researchers uncover novel species, functional
genes, and metabolic pathways. Metagenomics has applications in
environmental monitoring, bioremediation, and understanding microbial
diversity.

9. Bioinformatics Databases
 GenBank, UniProt: Comprehensive
repositories of genetic sequences and protein
information.
 DrugBank: Contains detailed drug data,
including drug targets, interactions, and
pharmacological properties.
 EMBL: Provides information on bioactive
molecules, including drug-like compounds and
their targets.

10. Sequence Analysis
 BLAST (Basic Local Alignment Search Tool): Compares sequences
against a database to identify homologous genes and proteins.
 InterProScan: Predicts protein function and domain architecture using
protein sequence signatures and profiles.

11. HOW ARE DRUGS DISCOVERED AND
DEVELOPED?
Microbes Laboratory
Drugs

13. STEPS
 The first step in the discovery of a drug is identification of the biological
origin of a disease, and the potential targets for intervention.
 Target identification starts with isolating the function of a possible
therapeutic target (gene/nucleic acid/protein) and its role in the disease.
 Identification of the target is followed by characterization of the
molecular mechanisms addressed by the target.
 For virtual screening computational methods including molecular
docking and molecular dynamics simulations are used.
 Lead optimization is the process by which a drug candidate is designed
after an initial lead compound is identified

14. The Future of Microbial Drug Discovery: Excitement
and Challenge
Exploring Extreme Environments and Uncultured Microbes:
Excitement: Microbes thrive in a vast array of extreme environments, from boiling
hot springs to the icy depths of the ocean. These "extremophiles" possess unique
adaptations and metabolic pathways, potentially harboring novel biomolecules with
unique properties. Exploring these environments using advanced techniques like
metagenomics could unlock a treasure trove of new drug leads.
Challenges: Accessing and culturing extremophiles can be difficult due to their
harsh habitats. Metagenomics analysis requires advanced computational tools and
expertise to navigate the complex data.

15. Additional Exciting Frontiers:
 Machine Learning & AI: These tools can accelerate drug discovery by
analyzing vast genomic datasets, predicting biomolecule properties, and
guiding target selection.
 Microbiome Research: Understanding the complex interactions between
microbes and our bodies offers opportunities to develop personalized
medicine and microbiome-based therapeutics.
Challenges:
 Funding and Investment: Despite the potential, microbial drug
discovery often faces challenges in securing funding compared to
traditional approaches.
 Regulatory Landscape: Regulatory frameworks need to adapt to
accommodate the unique nature of microbial-derived drugs and synthetic
biology approaches.

16.  High failure rates and lengthy
development times.
 Limited target identification and lack
of novel mechanisms.
 High costs and increasing regulatory
hurdles
Limitations

17. Conclusion
Overall, the future of microbial drug discovery holds
immense promise, offering exciting opportunities to combat
existing and emerging diseases with novel and sustainable
solutions. Addressing the challenges through collaborative
efforts and continued innovation will be crucial to unlock the
full potential of this field.

18. THANK YOU

19. Microbiology by Lansing M. Prescott, A TEXTBOOK OF PHARMACEUTICS- I by Mr. Ankur Agrawal,
NCBI
1. Jethwa, A., Bhagat, J., George, J., & Shah, S. (2023). Metagenomics
for Drug Discovery (pp. 125–153). https://doi.org/10.1007/978-981-99-5281-
6_6
2. Kandi, V., Suvvari, T. K., Vadakedath, S., & Godishala, V. (2021). Microbes,
Clinical trials, Drug Discovery, and Vaccine Development: The Current
Perspectives. Borneo Journal of Pharmacy, 4(4), 311–323.
https://doi.org/10.33084/bjop.v4i4.2571
3. Rahgu K, Shifali Choudhary, Triyugi Narain Kushwaha, Shashank Shekhar,
Shambhavi Tiwari, Sheikh, I. A., & Srivastava, P. (2023). Microbes as a
Promising Frontier in Drug Discovery: A Comprehensive Exploration of
Nature’s Microbial Marvels. https://doi.org/10.5281/ZENODO.8149064
4. Simpson, A. (2023). Challenges and Opportunities for Bioactive Compound
and Antibiotic Discovery in Deep Space. Journal of the Indian Institute of
Science, 103. https://doi.org/10.1007/s41745-023-00385-6
References