Where Antibiotics Come From: Mining Microorganisms for Medicines and Useful Lab Tools
by Simon Currie
In “Through the Looking-Glass” the Red Queen tells Alice “Now, here, you see, it takes all the running you can do, to keep in the same place.” This line inspired evolutionary biologist Leigh Van Valen to propose the Red Queen hypothesis which states that species must constantly adapt, evolve, and change simply to survive while pitted against other ever-evolving opposing species.
Antibiotics are, essentially, a chemical warfare tool in the never-ending struggle to survive for bacteria and other microorganisms. These organisms produce antibiotics to attack and defend against their competitors for space and resources.
So where do the antibiotics we use come from?
Most antibiotics we use today come from natural organisms such as bacteria, yeast, or other microorganisms, or are slight chemical modifications of natural antibiotics. So, the antibiotics we use as medicines and as lab tools are borrowed, or inspired, from the arsenal of ancient microbes!
That’s why most antibiotics were discovered in the natural world from such microorganisms or are slight variations of natural products.
Although it is not the focus of this article, this constant race to keep up continues in the clinical use of antibiotics as critical life-saving medicines. There, pathogens are developing resistance to widely-used antibiotics, necessitating the discovery of new antibiotics to keep apace.
Discovery of penicillin
The discovery of penicillin highlights both where many antibiotics come from and the, oftentimes, serendipitous nature of scientific discovery.
Alexander Fleming had just returned from summer holiday in 1928 and was sorting through petri dishes growing Staphylococcus bacteria. One plate looked peculiar. This plate had been contaminated and there was mold called penicillium growing on the plate. Interestingly, there was a bacteria-free halo around the mold (Figure 1). It was as if the mold had a magic force field that prevented bacteria from growing nearby.
Figure 1. Penicillium on Fleming’s petri dish prevented growth of bacterial colonies nearby.
This magic force field that repelled bacteria growth was powered by antibiotic molecules they called “penicillin” secreted by the mold. Fleming found that this mold juice was effective at killing a wide range of pathogenic bacteria including Streptococcus, Meningococcus, and the diptheria Bacillus (Fleming, 1929).
It proved difficult for Fleming and his colleagues to isolate penicillin from the “mold juice,” because they found it was rather unstable during process of trying to purify it.
Another group of researchers, spearheaded by Howard Florey, Ernst Chain, and Norman Heatley successfully isolated penicillin. While they also made technical innovations in isolating penicillin, a big key to their success was using brute force to scale up the starting material.
They would process up to 500 liters a week of mold filtrate! The demand for penicillin increased as World War II ramped up, and national labs and pharmaceutical companies in the United States played crucial roles in making the fermentation of penicillium and the production of penicillin more efficient (ACS, n.d.).
We know now that penicillin works against so many bacteria because it interferes with the synthesis of their outer cell wall. Over the years additional, very similar antibiotics have been made by retaining the active core of penicillin and chemically modifying parts of the molecule to give the resulting antibiotics new properties. Examples of these modified penicillins include:
This extensive list shows how a natural antibiotic can serve as a powerful starting point for developing related antibiotics with custom properties.
For example, ampicillin is more broadly active compared to penicillin, including some gram-negative bacteria. Amoxicillin is better absorbed through the digestive track relative to penicillin, making it more useful as an outpatient antibiotic that you can drink. These examples illustrate how slight changes to antibiotics influence their activity against different microorganisms, and how the antibiotic is absorbed and metabolized by humans or other host organisms.
Role of antibiotics in their natural environment
While penicillium serendipitously popped up on Fleming’s petri dish, scientists often have to leave the lab and look out in the natural world for sources of new antibiotics. They take samples from the soil from environments such as places like the Atacama Desert, from the ocean, from fossils, and even from animals (Adnani et al, 2017; Baranova et al, 2023; Cal Poly, 2025; von Bubnoff, 2006).
Basically, anywhere there are microorganisms growing and competing for resources, there will be antibiotics.
Outside of the lab, microorganisms use antibiotics to fend off antagonistic enemies and to cooperate with friends (symbionts) in the never-ending battle for limited resources and space.
While it seems obvious how antibiotics are used to kill, or stall enemies, how does a microorganism prevent friendly fire on cooperating friends and themselves?
To do this, microorganisms harbor a resistance plasmid, which enables them to grow even in the presence of a particular antibiotic. These resistance plasmids usually express enzymes that degrade or otherwise modify antibiotics so that they are no longer toxic to the host cell (Figure 2).
Figure 2. Active antibiotics (left) are neutralized by enzymes that modify the antibiotic into slightly different chemical forms that are inactive (right). Example modifications include acetylation, deamination, and phosphorylation.
Cooperating species share the resistance plasmid so that spewing out the antibiotic won’t harm their friends (Figure 3). This, at least for some time, enables microorganisms to differentiate between friend and foe.
Figure 3. Bacteria with plasmids that carry resistance genes are shared between cooperating microorganisms, allowing them to grow in the presence of the antibiotic that will ward off competing species.
But remember the never-ending pressure to evolve and survive? While a competing species is sensitive to an antibiotic, any species that produces that antibiotic will have the upper hand in battle.
However, if the sensitive species acquires the resistance gene, it will no longer be affected by that antibiotic and will be able to, again, successfully compete for food and territory. These molecular events form the basis of the back-and-forth frontline between different species.
This tremendous pressure to develop new weapons, and defense mechanisms that compels the development of even newer weapons, is why so many antibiotics have been discovered from various organisms. Beyond penicillin, antibiotics discovered in nature include:
While this list is not intended to be comprehensive, it shows that many antibiotics are discovered in the natural world, or developed based on a closely-related natural product.
Difficulties in finding new antibiotics
One of the biggest difficulties in producing antibiotics is culturing enough of the producing microorganism to generate sufficient quantities of the antibiotic for testing. For example, over 99% of bacteria isolated from soil cannot be cultured in labs (von Bubnoff, 2006).
Thinking about their natural environment can provide hints into how you might adjust your culturing strategy to help finicky microorganisms grow, though this a tedious process with low probability of success.
As one example of culturing optimization, my friend in graduate school Thomas Kakule was culturing a fungus sample isolated from the mountains of Nepal. This culturing process required growing the fungus on corn grit agar plates which are essentially agar plates with corn meal mixed in.
The fungus repeatedly failed to grow on plates made with the corn meal agar he had purchased from a reputable scientific supplier. Attempting to grow each culture was a 3-week process, so these repeated failures set him back nearly a month each time.
Eventually, Kakule suspected there was something in the corn meal agar that was preventing the fungus from growing. So, he went to the grocery store, bought organic corn meal with his own money, and made the media for corn grit agar plates from scratch. This worked; the Nepalese fungus finally grew, and he was able to finish his experiments (Kakule et al, 2015).
This example, as well as the fermentation of penicillium, represent cases from the less than 1% of the time that culturing exotic microorganisms in lab works.
However, in the vast majority of cases researchers are unable to find a suitable context for culturing natural microbes in the lab, making the isolation and production of potential antibiotics technically infeasible. These challenges, and the immense work it takes to overcome them, are all the more reason to appreciate and celebrate the antibiotics that have been successfully developed.
By the way, while I’ve framed this overall process in the context of antibiotic development, this same approach is used to identify, isolate, and optimize other bioactive natural products which has led to the discovery of novel pain medicines, chemotherapies, and more (Atanasov et al, 2021).
At GoldBio we have a vast catalog of high-quality and affordable antibiotics and related reagents – check out our website catalog and the link below to check those out. And if you discover a new antibiotic, there’s a good chance we’ll carry that one in the future too!
References
Adnani, N., Chevrette, M. G., Adibhatla, S. N., Zhang, F., Yu, Q., Braun, D. R., Nelson, J., Simpkins, S. W., McDonald, B. R., Myers, C. L., Piotrowski, J. S., Thompson, C. J., Currie, C. R., Li, L., Rajski, S. R., & Bugni, T. S. (2017). Coculture of Marine Invertebrate-Associated Bacteria and Interdisciplinary Technologies Enable Biosynthesis and Discovery of a New Antibiotic, Keyicin. ACS chemical biology, 12(12), 3093–3102. https://doi.org/10.1021/acschembio.7b00688
American Chemical Society International Historic Chemical Landmarks. (n.d.). Discovery and development of penicillin. Retrieved September 15, 2026, from https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html
Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., International Natural Product Sciences Taskforce, & Supuran, C. T. (2021). Natural products in drug discovery: advances and opportunities. Nature reviews. Drug discovery, 20(3), 200–216. https://doi.org/10.1038/s41573-020-00114-z
Baranova, M. N., Pilipenko, E. A., Gabibov, A. G., Terekhov, S. S., & Smirnov, I. V. (2023). Animal Microbiomes as a Source of Novel Antibiotic-Producing Strains. International journal of molecular sciences, 25(1), 537. https://doi.org/10.3390/ijms25010537
Cal Poly University Communications and Marketing. (2025, November 12). Cal Poly scientists look to ancient microbes to discover the antibiotics of the future. https://ucm.calpoly.edu/news/cal-poly-scientists-look-ancient-microbes-discover-antibiotics-future
Fleming A. (1929). On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ. British journal of experimental pathology, 10(3), 226–236.
Kakule, T. B., Zhang, S., Zhan, J., & Schmidt, E. W. (2015). Biosynthesis of the tetramic acids Sch210971 and Sch210972. Organic letters, 17(10), 2295–2297. https://doi.org/10.1021/acs.orglett.5b00715
von Bubnoff A. (2006). Seeking new antibiotics in nature's backyard. Cell, 127(5), 867–869. https://doi.org/10.1016/j.cell.2006.11.021
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