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Posts by Gavin Williams

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Development of a transcription factor-based biosensor strain for reporting α-terpineol production via the alcohol-dependent hemiterpene pathway in Escherichia coli Terpenes constitute a vast and industrially important class of natural products. Yet, microbial production of many high-value terpenoids remains limited by the difficulty of rationally engineering the...

Huge congratulations to lead author Catherine Odhiambo and co-author Isaac Ali on this beautiful work! Published in RSC Chemical Biology 🎉
Full paper (open access): pubs.rsc.org/en/content/a...

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The Bigger Picture: Terpenes are one of the largest and most diverse families of natural products — including medicines, vitamins, flavors, and fragrances. Tools like this biosensor accelerate the engineering of microbes to produce them sustainably at scale.

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Why It's Exciting: This is the first biosensor for monocyclic monoterpene alcohols — a class of molecules with major pharmaceutical, flavor, and fragrance applications. Its modular design allows it to be adapted to find and optimize the production of many other valuable products

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The Full System: We then coupled the biosensor to a complete α-terpineol biosynthetic pathway in E. coli, feeding the bacteria simple alcohol precursors and watching them make the fragrance molecule — confirmed by both the fluorescent signal and traditional analysis (GC-MS). ✅

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The Engineering: We started with a natural transcription factor that detects a different molecule, and used modeling + directed evolution to reshape its binding pocket so it recognizes α-terpineol. Just 3 rounds gave us a biosensor with a 22× improvement in sensitivity. 🎯

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Testing thousands of variants one by one using traditional methods is way too slow. The Solution: We built a genetic circuit inside E. coli that produces green fluorescent protein whenever the bacteria make α-terpineol. This lets us screen thousands of variants rapidly.

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The Problem: Currently, α-terpineol is produced industrially using harsh acids with low yields. We want bacteria to make it instead — cleaner, greener, scalable. But how do we know when the engineered microbe is actually doing its job?

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New paper from the Williams lab! We engineered bacteria that glow 🟢 when they make a valuable terpene alcohol. Why does that matter? Thread 👇 pubs.rsc.org/en/content/a... @ncstatechem.bsky.social

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Excited to share our #polyketide #biosensor artwork featured on the cover of Biochemistry! Thanks to several group members for your help with this! #MyACSCover

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Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation CoA thioesters are valuable intermediates in numerous biosynthetic routes and metabolic processes. However, diversifying these compounds and their corresponding downstream products hinges on broadenin...

pubs.acs.org/doi/full/10....

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Thrilled to share our latest enzyme engineering in ACS Chemical Biology! We improved an enzyme involved in #polyketide starter unit biosynthesis and used it to generate polyketide acceptor substrates in vitro. Kudos to Jared and the team of authors! @pubs.acs.org

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Promiscuity of an Alcohol-Dependent Hemiterpene Pathway for the In Vivo Production of a Non-Natural Alkylated Tryptophan Derivative The prenyl motif determines the biological activity of many natural products. Yet, structural diversification of the prenyl site has been restricted due to the limitations of native biosynthetic pathw...

pubs.acs.org/doi/10.1021/...

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Excited to share our @pubs.acs.org Syn Bio publication on the production of non-natural alkylated Trp derivatives in E. coli. Potential applications for #terpene diversification. Kudos to everyone who contributed to this work.

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Directed Evolution of a Macrolide-Sensing Transcription Factor Biosensor for the Detection of Macrolactone Aglycones via “Effector Walking” and Efflux Pump Deletion Glycosylated macrolactones (macrolides) often display broad and potent biological activities and are targets for drug development and discovery. The modular genetic organization of macrolide polyketid...

I am thrilled to share our latest biosensor publication in ACS Biochemistry. In this work, we engineered a #biosensor strain for detecting polyketide macrolactones as a step toward applying high-throughput #synbio to polyketide synthases. pubs.acs.org/doi/10.1021/... @ncstatechem.bsky.social

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