Plastic is everywhere on Earth. Inside me, inside you, in the deepest ocean trenches and the highest mountain peaks. We’ve produced billions of tons of the stuff and we keep making more and more of it. We also can’t seem to get rid of plastic. Unexpectedly, the main advantage of plastic (its durability) has turned out to be its biggest problem.
Now, a team of scientists in Japan may start turning the tide. They’ve hijacked the metabolism of a common bacterium, Escherichia coli, turning it into a microscopic factory that brews a key ingredient for high-performance, biodegradable plastics directly from simple sugar.
In a new study published in Metabolic Engineering, researchers from Kobe University detail how they engineered a new biological pathway that produced the highest yield ever recorded for this promising compound, creating a viable blueprint for weaning one corner of the plastics industry off its dependence on oil.
A Better Recipe for a Greener Plastic
Many of the plastic bottles millions of people drink from every day are likely made of polyethylene terephthalate, or PET. PET is a polymer, meaning it’s a long chain of repeating molecular units, called monomers. One of the key monomers in PET is terephthalic acid, a chemical derived from petroleum. It’s this acid that makes the plastic strong and durable but also stubbornly non-biodegradable.
For years, scientists have been hunting for a bio-based replacement that could provide similar, or even better, properties.
One of the most promising candidates is a molecule called 2,5-pyridinedicarboxylate, or 2,5-PDCA. Like terephthalic acid, it can be used to synthesize polyesters and other high-strength polymers called polyimides. The crucial difference is the presence of a nitrogen atom in its core ring structure.
This seemingly small change has big implications, potentially leading to plastics with superior physical properties. This chemical change also opens the door to true biodegradability. The challenge, however, has always been making 2,5-PDCA efficiently and sustainably.
Chemical synthesis methods are often plagued by low yields. That’s where biology comes in. If we could get microbes to produce it for us, it would be fantastic. Of course, that’s easier said than done.
The Old, Inefficient Way
The original method started with a molecule called protocatechuate (PCA). The plan was to use an enzyme to break open PCA’s ring structure and then add a nitrogen atom (from ammonia) to form the desired 2,5-PDCA.
However, the problem was that the intermediate molecule created after breaking the ring was very unstable. Before it could grab a nitrogen atom, it would often fall apart and create many unnecessary byproducts. The whole process was very inefficient.
The Kobe University team, led by Dr. Shuhei Noda and Dr. Tsutomu Tanaka, decided to find a completely different route. They designed a new pathway that starts not with PCA, but with a related molecule called p-aminobenzoic acid, or PABA. Their strategy hinged on a key enzyme which they borrowed from another bacterial species. This means the crucial nitrogen is already part of the molecule before the ring is ever broken.
The result was a game-changer. The resulting product was stable and reliably snapped back into the correct 2,5-PDCA structure without losing parts of itself along the way.
To prove their new recipe was superior, the researchers ran a head-to-head comparison. They created two strains of E. coli. One used the old PCA pathway, and the other used their new PABA-derivative pathway. They fed each strain the respective starting material and measured the outcome. The results were stunningly clear, showing that the new method reliably creates a sturdy, biodegradable plastic.
Can We Create Microbial Plastic Factories?
Having a superior chemical recipe is a good start. Getting a living organism to execute it efficiently, starting from nothing but glucose, is an even more complex challenge.
Their first step was to turn E. coli into a PABA-making specialist. This involved clever and meticulous gene editing to ensure that the microbes can efficiently turn resources into plastic. It was a massive challenge with several bottlenecks, the most stubborn of which emerged when one of the enzymes they had introduced produced the highly reactive compound hydrogen peroxide, H2O2. The compound then attacked the enzyme that produced it, thereby deactivating it.
“Through refining the culture conditions, in particular by adding a compound that can scavenge H2O2, we could finally overcome the issue, although this addition may present new economic and logistical challenges for large-scale production,” says Kobe University bioengineer Tanaka Tsutomu, one of the study authors.
At the end, however, the researchers were able to control the process and scale it up. They moved the process from small test tubes to a controlled 1-liter bioreactor, a setup that allows for precise control over variables like pH, temperature, and dissolved oxygen.
The results were spectacular. Over the course of 144 hours (six days), the engineered E. coli culture grew robustly and steadily churned out the target molecule. This is the highest concentration and yield of 2,5-PDCA ever achieved through microbial fermentation.
A Promising Approach
This breakthrough represents a pivotal step toward the sustainable production of bio-based plastics. While challenges remain (especially when it comes to scale), this work establishes a powerful and efficient biological platform. This isn’t the first time researchers coerced microbes to produce plastic, but this is one of the most promising approaches.
By cleverly rewiring a microbe’s natural chemistry, the Kobe University team has demonstrated that the building blocks for the plastics of tomorrow may not come from an oil refinery, but from a bubbling vat of sugar-fed bacteria.
Journal Reference: A. Katano et al.: Biosynthesis of 2,5-pyridinedicarboxylate from glucose via p-aminobenzoic acid in Escherichia coli. Metabolic Engineering (2025). DOI: 10.1016/j.ymben.2025.08.011
