Synbio Breakthrough: Turning Plastic Bottles into Life-Saving Drugs!

Turning trash into medicine. Do I need to say anything else? Today’s paper is a cool one! Mixing synthetic biology and traditional chemistry for an amazing result.

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Plastic Bottles to Drugs

The Promises of Synthetic Biology

Synthetic biology, or just SynBio for the cool kids, has big ambitions.

It promises to reprogram biology to solve lots of problems: energy generation, drug production, new foods or biosensors. The sky is the limit! And maybe not even, there are SynBio experiments going on on the ISS as well!

One particular urgent target is bioremediation, which uses bacteria, plants or enzymes to fix human pollution.

And do you know what we have made a lot of? Plastics, especially single-use PET. Yes, the one used for water bottles. And the numbers are insane: we produce 56 million tons of PET every year! 80% of it is single-use, and 24 million tons end up incinerated or in landfills! I founded a startup in this space before; we need solutions here.

The Limitations of Living Systems

SynBio tries, but it still has limitations here:

• Biological systems are hard to engineer, with lots of things to balance at the same time: production, metabolism, growth, side products, and even more!

• The chemical space in biological systems is limited to reactions that have evolved (although systems like designed enzymes are helpful here!)

• We don’t know enough to simply drop in a new synthetic pathway! Every time, there is something new that comes up.

All of this is because we are working with living systems, which we don’t have control over (although artificial cells could fix this!).

But do you know what we know very well, by now? Chemistry! Chemical synthesis practically created the world we live in, for example, the plastics we talked about earlier. And scientists are very good at chemistry.

So, an alternative for SynBio is to translate classic synthetic chemistry reactions and interface them with biological metabolism. These biocompatible reactions would let scientists take advantage of the versatility of chemical reactions while reducing the problems with biological systems! A win-win situation.

Unfortunately, there are not a lot of biocompatible reactions available, yet.

Translating Reactions for Bacteria

Enter today’s paper. The team focused on making a biocompatible version of the Lossen rearrangement. This valuable reaction is used to create pharmaceutical and agrochemical molecules, and it converts activated hydroxamates into primary amines (or at least, that’s what my chemistry friends say. I trust them).

Traditionally, this reaction requires heat or metals, and it proceeds in harsh conditions where bacteria would die. Their aim was to create a version of this reaction that works in E. coli under ambient conditions, without being toxic to the cells!

So, what did they do?

The team designed a substrate (O-Piv benzhydroxamate, for the more chemistry-inclined) that, after Lossen rearrangement, releases para-aminobenzoic acid (PABA), an essential metabolite for bacterial growth. No PABA, no growth!

Then, the team used the oldest trick in the microbiology book. Using a PABA-deficient E. coli strain, they showed that when the synthetic substrate was added, the bacteria started to grow. That meant:

1. The rearrangement was working

2. It wasn’t toxic for the cells!

The funny part is, they screened 10 metal catalysts for the reaction. Surprisingly, they all worked, but the control without any added catalysts also worked! It turns out the rearrangement can be catalyzed by phosphates already present in the growth media, so no other catalysts are required. Serendipity at work here!

So, at this point, they had a simple way to interface the Lossen rearrangement with cells. But they wanted more.

Feeding Bacteria With Plastic

They realized that they could derive their substrate from PET as well. So, they started working on breaking PET down, and then they fed the PET-derived substrate to E. coli. Lo and behold, the PABA-deficient E.coli still grew! Apparently, bacteria don’t care where their food comes from.

This was a solid proof-of-concept for microbial PET bioremediation. And if you thought the team was done, well, you would be sorely mistaken.

Turning Bottles into Paracetamol

Growing bacteria on waste material is, of course, valuable, but do you know what’s even more valuable? Paracetamol, the first-line WHO-recommended treatment for pain and fever. This drug is currently derived from phenol, which is in turn derived from fossil fuels. 

So, the team engineered E. coli to synthesise paracetamol starting from PABA. After some optimization, they got there. The bacteria-produced paracetamol, with:

• 100% yield when starting from PABA

• Over 90% starting from the PET-derived substrate!

And all of this by interfacing a biocompatible reaction with a two-gene pathway in bacteria!

Future Work and Possibilities

This work shows that biocompatible chemistry has its place in SynBio!

It’s a powerful complement to enzyme design and engineered pathways, allowing versatility similar to organic chemistry in greener ways. The authors aim to figure out how to scale this method, and then see if it’s actually greener than the alternatives. Sometimes these calculations can get a bit tricky!

But I’m confident that this innovation will move SynBio forward! Synbio is often caught between two extremes: either making expensive, niche, high-margin products, but they don’t really move us away from traditional production, or trying (and failing) to compete with bulk chemistry.

This work combines the best of both worlds: a valuable, high-volume product! We’ll see, but I’m excited! Come on, turning trash into medicine?

And if you want more info, especially about the chemistry part, go here and have a great read!

If you made it this far, thank you! Do you see a future for SynBio? Are you burned from previous failures? What do you think could be the next big target? Reply and let me know!

More Room:

• Overloading DNA Sensors: Now, no one likes to use more DNA. But sometimes it’s useful! This study introduces a "decoy DNA" strategy to protect DNA-based molecular probes from DNase degradation in live-cell environments. By adding excess unmodified double-stranded DNA, the decoys outcompete functional probes for DNase binding, extending probe stability from just 1–2 hours to over 24 hours. This method is simple, cost-effective, and easily integrated into existing systems!

• Missing DNA Delivery? If you feel like there wasn’t enough nucleic acid delivery in your life, rejoice! This viewpoint highlights the latest advances and challenges in nucleic acid delivery technologies, essential for therapies like gene editing and RNA-based drugs. Experts across platforms share insights on how their systems offer tunable, biologically responsive solutions. They also discuss key hurdles like targeting, stability, and immune response, shaping the future of effective and safe nucleic acid delivery. It’s super cool!

• More CRISPR Uses:  Gene editors can have a lot of uses, not only to modify genomes. This study presents smLiveFISH, a CRISPR–Csm-based method for real-time imaging of unmodified RNA at the single-molecule level in live cells. It enables tracking native transcripts like NOTCH2 and MAP1B, revealing their distinct localization behaviors. This technique opens new avenues for studying RNA dynamics in health and disease.

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