Plate Nº 36 · recorded October 10, 2026
Chemistry & MaterialsReported finding
Evolved Enzymes Build TB Antibiotic Ingredient Without the Waste
Caltech researchers using Nobel laureate Frances Arnold's directed evolution have made only the active mirror-image form of a key TB antibiotic building block, potentially halving waste and cutting costs.
By Priya Raman4 min read745 words
In brief
- The study was published in Nature on Sept. 23 by Ziqi Li and colleagues in Frances Arnold's Caltech lab.
- Only the (S) mirror-image form of oxazolidinone antibiotics kills bacteria; standard synthesis wastes half of each batch.
- The team screened several hundred enzymes from a library of more than 5,000 before improving one through directed evolution.
- Frances Arnold won the 2018 Nobel Prize in Chemistry for developing directed evolution in the early 1990s.
- More than 80% of TB cases occur in low- and middle-income countries, where drug-resistant strains are rising.
Half of every batch of certain tuberculosis antibiotics is normally wasted because the drugs come as a mixture of two mirror-image molecules — and only one of them kills bacteria. On Sept. 23, a team led by Nobel laureate Frances Arnold at Caltech published a method in Nature that produces only the useful form, a step that could eventually cut manufacturing costs for drugs needed most in low-income countries.
Tuberculosis is a contagious bacterial infection that mainly attacks the lungs. Treatments exist, but more than 80% of cases occur in low- and middle-income nations, where drug-resistant strains are spreading and medication costs strain health systems. A newer class of antibiotics, called oxazolidinones, has shown promise against multidrug- and extensively drug-resistant TB — yet its production cost keeps it out of reach for many of the countries that need it most.
"In our lab, we use enzymes—nature's catalytic machinery—to make valuable molecules in a more efficient and sustainable way," says Ziqi Li, a postdoctoral scholar in Arnold's group and lead author of the study. "We wanted to find a more accessible route to making effective antibiotics against TB."
Why do mirror images matter?
Many drug molecules can exist in two mirror-image forms, like a left hand and a right hand. Both contain exactly the same atoms, but at one key point — called a stereogenic center — those atoms sit differently in three-dimensional space. That arrangement shapes how the molecule interacts with proteins and other biomolecules in the body.
The researchers targeted a compound called 5-(S)-aminomethyl oxazolidinone, a building block with wide pharmaceutical use, including antibiotics that disrupt bacterial cell growth. For oxazolidinones, only the (S) form kills bacteria. Manufacturers typically produce a 50-50 mixture of the two forms, so half of each batch is unusable waste.
Li and colleagues set out to build the stereogenic center from scratch with enzymes, producing only the (S) form. Success here could raise yields and, in turn, lower costs.
How did the team evolve the right enzyme?
The team did not start from nothing. "We have more than 5,000 enzymes in our freezer, so we went digging into those libraries, screened a few hundred, and found one that gave us a starting point," Li says. "It wasn't necessarily a very good starting point, but we iteratively improved this enzyme to ultimately get to a final point where it's high yield and high selectivity."
The improvement relied on directed evolution, the bioengineering method Arnold developed in the early 1990s and which earned her the 2018 Nobel Prize in Chemistry. The workflow is straightforward:
- Induce mutations in the gene encoding a chosen enzyme.
- Produce thousands of mutated enzyme variants.
- Test the array for a desired trait.
- Select the top performers and repeat the cycle.
"The vast and wonderful chemistry of life is a result of billions of years of enzyme evolution, which is still ongoing," says Arnold, Caltech's Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry and director of the Donna and Benjamin M. Rosen Bioengineering Center. "But with these tools, we can make enzymes that do so much more efficiently and with little waste, reducing the cost of producing what we need for our daily lives."
Does this mean cheaper TB drugs soon?
Not yet — and the researchers are careful to say so. The new method is a strategy for efficiently synthesizing 5-(S)-aminomethyl oxazolidinone antibiotics, covering both clinically relevant and discovery-stage versions, while reducing waste. But mass production remains an open question.
"We solved the first step to prove that the enzymes can make these molecules," Li says. "But there's still a very long way to go before we know whether it is possible to produce it in mass quantities. However, this proof-of-concept work is an important step forward in making medications that are both effective and more affordable."
Li hopes pharmaceutical companies will take the findings and refine the method further. The paper, "Chiral oxazolidinones via biocatalytic aziridination of unactivated alkenes," appears in Nature (DOI: 10.1038/s41586-026-11169-0), with Li as first author alongside colleagues in Arnold's group.
For now, the work stands as a laboratory proof of concept: enzymes, evolved in Pasadena, building the exact molecular handedness that TB drugs require. Whether that translates into affordable medicine on pharmacy shelves in Lagos or Dhaka will depend on the scaling work that comes next.
via Phys.org Chemistry (Source)
More from Priya Raman
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Senior reporter covering industry trends and analytics at SciBeat.
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