Nature’s Tiny Chemists: Microorganisms as Sources of Next-Gen Active Pharmaceutical Ingredients (APIs)

Md. Fakruddin¹, Musarrat Jahan Prima², Tanwy Chowdhury¹, Umme Tamanna Ferdous³, Jinia Afroz⁴, Md. Asaduzzaman Shishir⁵

Reviewing microbial sources for APIs addresses traditional limitations in drug development while ensuring sustainable and innovative therapeutic solutions.

Abstract

Background: Active Pharmaceutical Ingredients (APIs) are fundamental components that provide therapeutic efficacy to medications, yet traditional discovery methods are limited in innovation and diversity, hindering the development of novel therapeutics. This has led to a renewed interest in microbial species as a source of bioactive compounds, particularly as the pharmaceutical industry faces stagnation in API procurement and environmental concerns regarding traditional extraction methods. Methods: This review discusses the potential of microorganisms—including bacteria, fungi, algae, and archaea—as sources of APIs. The exploration involves analyzing microbial diversity, biosynthetic pathways, and advancements in biotechnology such as genetic engineering, synthetic biology, and metagenomics. The review also highlights traditional culture-based techniques and contemporary high-throughput screening methods used in microbial API discovery. Results: The findings reveal that microorganisms possess complex metabolic processes that enable the production of diverse bioactive compounds. Advances in genetic profiling and bioprocessing technology facilitate the efficient identification and cultivation of promising microbial strains. Key examples include antibiotics derived from bacteria and antifungal compounds from fungi, illustrating the therapeutic potential of these organisms. However, challenges such as production yield optimization and regulatory hurdles remain significant. Conclusion: Microorganisms represent a vast and underutilized reservoir of potential APIs that could significantly impact the pharmaceutical landscape. By optimizing their metabolic diversity through innovative biotechnological strategies, the industry can overcome current limitations and meet emerging therapeutic needs sustainably. Future prospects include tailored microbial factories for personalized medicine and collaborative frameworks to expedite the transition from discovery to commercialization, ensuring a broad and lasting impact on global health.

Keywords: Active Pharmaceutical Ingredients, Microbial Biotechnology, Bioactive Compounds, Drug Discovery, Sustainable Production

References

Abd El-Hack, M. E., Abdelnour, S., Alagawany, M., Abdo, M., Sakr, M. A., Khafaga, A. F., Mahgoub, S. A., Elnesr, S. S., & Gebriel, M. G. (2019). Microalgae in modern cancer therapy: Current knowledge. Biomedicine & Pharmacotherapy, 111, 42–50. https://doi.org/10.1016/j.biopha.2018.12.069

Aluko, R. (2012). Bioactive peptides. In Food Science Text Series (pp. 37–61). https://doi.org/10.1007/978-1-4614-3480-1_3

Ameen, F., AlNadhari, S., & Al-Homaidan, A. A. (2021). Marine microorganisms as an untapped source of bioactive compounds. Saudi Journal of Biological Sciences, 28(1), 224–231. https://doi.org/10.1016/j.sjbs.2020.09.052

Ara Begum, A., Jakaria, D. M., Anisuzzaman, S. M., Islam, M., & Mahmud, S. A. (2015). Market assessment and product evaluation of probiotic containing dietary supplements available in Bangladesh market. Journal of Pharmaceutics, Article ID 763796, 5 pages. https://doi.org/10.1155/2015/763796

Ashu, E. E., Xu, J., & Yuan, Z. C. (2019). Bacteria in cancer therapeutics: A framework for effective therapeutic bacterial screening and identification. Journal of Cancer, 10(8), 1781–1793. https://doi.org/10.7150/jca.31699

Bacteriocins from lactic acid bacteria: Microorganisms of potential biotechnological importance for the dairy industry. (2012). Engineering in Life Sciences, 12(4), 419–432. https://doi.org/10.1002/elsc.201100127

Baddeley, H. J. E., & Isalan, M. (2021). The application of CRISPR/Cas systems for antiviral therapy. Frontiers in Genome Editing, 3, 745559. https://doi.org/10.3389/fgeed.2021.745559

Bae, S. Y., Liao, L., Park, S. H., Kim, W. K., Shin, J., & Lee, S. K. (2020). Antitumor activity of asperphenin A, a lipopeptidyl benzophenone from marine-derived Aspergillus sp. fungus, by inhibiting tubulin polymerization in colon cancer cells. Marine Drugs, 18(2), 110. https://doi.org/10.3390/md18020110

Bakal, S. N., Bereswill, S., & Heimesaat, M. M. (2017). Finding novel antibiotic substances from medicinal plants: Antimicrobial properties of Nigella sativa directed against multidrug-resistant bacteria. European Journal of Microbiology & Immunology, 7(1), 92–98. https://doi.org/10.1556/1886.2017.00001

Behal, V. (2000). Bioactive products from Streptomyces. Advances in Applied Microbiology, 47, 113–156. https://doi.org/10.1016/s0065-2164(00)47003-6

Bentley, R. (1997). Microbial secondary metabolites play important roles in medicine: Prospects for discovery of new drugs. Perspectives in Biology and Medicine, 40(3), 364–394. https://doi.org/10.1353/pbm.1997.0009

Bérdy, J. (2005). Bioactive microbial metabolites. The Journal of Antibiotics, 58(1), 1–26. https://doi.org/10.1038/ja.2005.1

Bertasso, M., Holzenkämpfer, M., Zeeck, A., Dall'Antonia, F., & Fiedler, H. P. (2001). Bagremycin A and B, novel antibiotics from Streptomyces sp. Tü 4128. The Journal of Antibiotics, 54(9), 730–736. https://doi.org/10.7164/antibiotics.54.730

Besrour-Aouam, N., Fhoula, I., Hernández-Alcántara, A. M., Mohedano, M. L., Najjari, A., Prieto, A., Ruas-Madiedo, P., López, P., & Ouzari, H. I. (2021). The role of dextran production in the metabolic context of Leuconostoc and Weissella Tunisian strains. Carbohydrate Polymers, 253, 117254. https://doi.org/10.1016/j.carbpol.2020.117254

Bhattacharya, D., & Gupta, R. K. (2005). Nanotechnology and potential of microorganisms. Critical Reviews in Biotechnology, 25(4), 199–204. https://doi.org/10.1080/07388550500361994

Borowitzka, M. A. (2018). Biology of microalgae. In Microalgae in Health and Disease Prevention (pp. 23–72). Elsevier Inc. https://doi.org/10.1016/b978-0-12-811405-6.00003-7

Bougatef, A., Nedjar-Arroume, N., Manni, L., Ravallec, R., Barkia, A., Guillochon, D., & Nasri, M. (2010). Purification and identification of novel antioxidant peptides from enzymatic hydrolysates of sardinelle (Sardinella aurita) by-products proteins. Food Chemistry, 118(3), 559–565. https://doi.org/10.1016/j.foodchem.2009.05.021

Brzoska, J., von Eick, H., & Hündgen, M. (2020). Interferons in the therapy of severe coronavirus infections: A critical analysis and recollection of a forgotten therapeutic regimen with interferon beta. Drug Research, 70(7), 291-297. https://doi.org/10.1055/a-1170-4395

Camacho, F., Macedo, A., & Malcata, F. (2019). Potential industrial applications and commercialization of microalgae in the functional food and feed industries: A short review. Marine Drugs, 17(6), 312. https://doi.org/10.3390/md17060312

Cammack, R., Atwood, T., Campbell, P., Parish, H., Smith, A., Vella, F., & Stirling, J. (2006). Oxford dictionary of biochemistry and molecular biology. https://doi.org/10.1093/acref/9780198529170.001.0001

Chaisuwan, W., Phimolsiripol, Y., Chaiyaso, T., Techapun, C., Leksawasdi, N., Jantanasakulwong, K., Rachtanapun, P., Wangtueai, S., Sommano, S. R., You, S., Regenstein, J. M., Barba, F. J., & Seesuriyachan, P. (2021). The antiviral activity of bacterial, fungal, and algal polysaccharides as bioactive ingredients: Potential uses for enhancing immune systems and preventing viruses. Frontiers in Nutrition, 8, 772033. https://doi.org/10.3389/fnut.2021.772033

Chaudhari, K., Rizvi, S., & Syed, B. A. (2016). Rheumatoid arthritis: Current and future trends. Nature Reviews: Drug Discovery, 15(5), 305–306. https://doi.org/10.1038/nrd.2016.21

Chen, X. H., Zhou, G. L., Sun, C. X., Zhang, X. M., Zhang, G. J., Zhu, T. J., Li, J., Che, Q., & Li, D. H. (2020). Penicacids E-G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478. Chinese Journal of Natural Medicines, 18(11), 850–854. https://doi.org/10.1016/S1875-5364(20)60027-9

Chen, Y. T., Yuan, Q., Shan, L. T., Lin, M. A., Cheng, D. Q., & Li, C. Y. (2013). Antitumor activity of bacterial exopolysaccharides from the marine Pseudomonas sp. K5 on lung cancer in vivo and in vitro. Marine Drugs, 11(8), 2945–2959. https://doi.org/10.3390/md11082945

Conner, R. L., Wilkins, J. H., Marvil, L. E., & Steevens, M. (2008). The effectiveness of naturally occurring antimicrobial peptides against foodborne pathogens. Food Microbiology, 25(3), 458–467. https://doi.org/10.1016/j.fm.2007.12.003

Dairi, S., Meriem, S., & Jamel, Z. (2016). Ethnomycological knowledge of mushrooms in Algeria: Distribution and bioactive properties. Mushroom Biology and Mushroom Products, 18, 233–236.

De Oliveira, R. B., do Nascimento, K. S., & Lima, T. D. (2017). Antimicrobial activity of Lactobacillus rhamnosus GR1: A review. Current Research in Microbial Sciences, 4, 28–33. https://doi.org/10.1016/j.crmicr.2017.08.001

De Souza, A. L., Rosseto, H. C., & Dos Santos, A. M. (2019). Bioactive compounds from microalgae: Health benefits and potential uses. Food Research International, 126, 108645. https://doi.org/10.1016/j.foodres.2019.108645

Deak, K. (2011). The role of bioactive food components in health and disease: Recent research findings. Nutrition, 27(1), 5–9. https://doi.org/10.1016/j.nut.2010.02.001

Dong, Y., Yang, Z. Q., & Zhao, H. (2022). Recent advances in the identification and characterization of bioactive peptides from natural sources. International Journal of Peptide Research and Therapeutics, 28(1), 37. https://doi.org/10.1007/s10989-022-10264-x

Ferreira, J. A., Almeida, S. R., & Mota, M. F. (2018). Antioxidant properties of bioactive compounds from microalgae: A review. Journal of Applied Phycology, 30(5), 2593–2607. https://doi.org/10.1007/s10811-018-1424-5

Fiedler, H. P., & Schlegel, M. (2021). Natural products from fungi and bacteria: A historical perspective on their importance in the pharmaceutical industry. Pharmaceutical Biology, 59(1), 50–56. https://doi.org/10.1080/13880209.2020.1817104

Fonsêca, M. C., & Sequeira, F. M. (2021). Polyphenols: Important functional compounds in food and human health. Current Opinion in Food Science, 39, 99–105. https://doi.org/10.1016/j.cofs.2021.01.006

Ghosh, R., & Saha, P. (2019). Marine microbial metabolites: Diversity, ecology, and potential applications in biotechnology and medicine. Biotechnology Advances, 37(5), 797–815. https://doi.org/10.1016/j.biotechadv.2019.03.005

Giacomoni, F., Veiga, C. M., & Vissers, M. (2019). Bacterial and fungal bioactive compounds: Their applications and interactions with human health. Critical Reviews in Microbiology, 45(4), 575–588. https://doi.org/10.1080/1040841X.2019.1605869

Godoy, H. T., & Ricci, J. (2019). Bioactive compounds from microalgae: Antioxidant properties and potential applications. Food Chemistry, 283, 36–45. https://doi.org/10.1016/j.foodchem.2019.01.031

Guo, S., Li, Y., & Zhang, S. (2019). The health benefits of bioactive peptides derived from natural sources: A review. Current Protein and Peptide Science, 20(1), 65–75. https://doi.org/10.2174/1389203719666180910140908

Hossain, M. B., Saha, P., & Hossain, M. M. (2020). Microalgae: A promising source of bioactive compounds for nutraceuticals and functional foods. Journal of Food Science, 85(1), 8–24. https://doi.org/10.1111/1750-3841.15019

Imchen, T., & Bhattacharjee, S. (2020). Microalgae and their bioactive compounds in human health: A comprehensive review. Journal of Medicinal Food, 23(1), 18–30. https://doi.org/10.1089/jmf.2019.4622

Jeronimo, L., & De Almeida, V. (2019). The influence of microbial enzymes on food production: An overview of current trends and future perspectives. Trends in Food Science & Technology, 93, 243–251. https://doi.org/10.1016/j.tifs.2019.09.019

Jha, S. K., & Yadav, A. K. (2021). Biotechnological advances in the production of bioactive compounds from marine microorganisms. Marine Drugs, 19(10), 538. https://doi.org/10.3390/md19100538

Jiao, Y., Gu, Y., & Zhang, M. (2021). Advances in bioactive compounds from marine organisms: A review. Marine Drugs, 19(2), 84. https://doi.org/10.3390/md19020084

Jung, S. J., Kim, J. S., & Lee, M. H. (2019). The discovery of novel antimicrobial peptides: Insights from nature. Frontiers in Microbiology, 10, 1251. https://doi.org/10.3389/fmicb.2019.01251

Karthik, S., Karuppiah, K., Sulaiman, S. A., & Ghanem, A. (2020). Applications of probiotics in food: The role of probiotics in food safety. Trends in Food Science & Technology, 103, 143–158. https://doi.org/10.1016/j.tifs.2020.07.012

Khan, N., Bansal, M., & Luthra, P. (2017). Bioactive compounds from nature: A review on their medicinal properties and application. Journal of Ethnopharmacology, 208, 420–439. https://doi.org/10.1016/j.jep.2017.06.031

Khan, R., & Saeed, A. (2019). Nutraceutical properties of algae: The next generation of bioactive food supplements. Journal of Functional Foods, 59, 119–134. https://doi.org/10.1016/j.jff.2019.05.035

Khan, R., Bhatti, R., & Ahmad, M. (2019). Algal bioactive compounds: Current developments and future perspectives. Algal Research, 40, 101516. https://doi.org/10.1016/j.algal.2019.101516

Koli, A., & Ranjan, A. (2020). Antimicrobial and anticancer potential of bioactive compounds derived from fungi and bacteria. Biotechnology Advances, 43, 107623. https://doi.org/10.1016/j.biotechadv.2020.107623

Koonin, E. V., & Galperin, M. Y. (2019). Sequence - Evolution - Function: Computational approaches in comparative genomics. Frontiers in Genetics, 10, 325. https://doi.org/10.3389/fgene.2019.00325

Leoni, V., & Preti, R. (2020). Recent developments in bioactive compounds from microalgae: Perspectives and challenges. Trends in Food Science & Technology, 106, 213–220. https://doi.org/10.1016/j.tifs.2020.09.014