Source: Advanced Science, by Jia Feng; Getao Liu; Ding Ma; Jiaxiang Yuan; Xinyi Zhang; Weihao Wang; Chen Ma; Yang Liao; Siyuan Gao; Lei Qin; Jiao Feng; Sheng Xu; Xin Wang; Kequan Chen (September 27, 2026). AI-generated summary by biochip.com, published . Not independently reviewed.
Key takeaways
- Nanjing Tech University and Tsinghua University developed a PpyrF-based biosensor that responds to cadaverine and related diamines.
- Biosensor-guided engineering increased E. coli cadaverine titer 44% to 114.2 g/L using exporter, pathway, and genome-scale screens.
- The study does not establish performance in industrial-scale fermentation or demonstrate the sensor in microbial hosts beyond E. coli.
Researchers at Nanjing Tech University and Tsinghua University built a genetically encoded diamine biosensor that detects cadaverine inside engineered Escherichia coli. They coupled the sensor to fluorescence-activated cell sorting, a method that rapidly separates brighter cells from dimmer ones, to find bacterial variants that made more of this industrial chemical. The work raised cadaverine production by 44% to 114.2 grams per liter, using the sensor to guide changes across transport, metabolic pathways, and the genome. It matters because screening large numbers of engineered microbes is often the bottleneck in developing biological routes to polymer ingredients.
A Sensor for a Difficult Molecule
Cadaverine is a diamine, meaning it has two nitrogen-containing amino groups. Despite its name, it is an important building block for polyamides and polyurethanes, classes of polymers used in durable materials. Microbes can make cadaverine from renewable feedstocks, but improving a strain typically requires testing many possible genetic changes.
The team focused on a common problem in metabolic engineering: researchers can now create huge libraries of altered cells, but often lack a fast way to identify the few that produce the most target chemical. A biosensor addresses that mismatch by converting an invisible chemical signal inside a cell into an observable output, in this case green fluorescent protein, or GFP.
Finding a Native Response
Rather than beginning with a known cadaverine detector, the researchers searched E. coli's own stress response. Earlier work had shown that cadaverine concentrations above 20 grams per liter markedly suppress the bacterium's growth. The team used transcriptomics, which measures changes in gene activity across the cell, to identify 669 genes whose expression changed significantly under high cadaverine exposure.
They attached promoters, DNA control regions that turn genes on or off, from the 50 most upregulated and 50 most downregulated genes to GFP. Testing this promoter library at different cadaverine concentrations identified PpyrF as a diamine-responsive promoter. Put simply, the promoter acted like a molecular switch whose output could be read as fluorescence.
Tuning the Biological Switch
The team investigated why PpyrF responded to cadaverine and related amines. Their results suggested a role for Ihfβ, a DNA-binding regulatory protein. Cadaverine and structurally related amines may activate the promoter by changing interactions between Ihfβ and DNA.
The researchers then improved the sensor step by step. They mutated the PpyrF DNA sequence, altered the Ihfβ sequence, and tuned the ribosome binding site, a genetic segment that helps control how much protein a cell makes. Together, these changes increased the biosensor's fold induction, the difference between its on and off signals, by more than 2.33-fold.
Screening for Better Producers
The optimized biosensor was integrated with fluorescence-activated cell sorting, or FACS. This approach works like sorting a mixed bag of colored beads at high speed: cells producing a stronger fluorescent signal can be isolated from a large population. Here, fluorescence served as a proxy for cadaverine production.
The team used the platform to tune a specific cadaverine exporter, optimize pathway variants from SCRaMbLE libraries, and search genome-wide for beneficial overexpression targets in the ASKA collection. SCRaMbLE is a method for rearranging DNA segments to generate many genetic combinations. Those iterative screens pointed to biofilm formation and altered carbon flux, the routing of cellular carbon through metabolism, as important contributors to higher cadaverine output.
Why This Matters
Cadaverine has potential as a bio-based polymer monomer, but high-performing microbial producers require more than adjusting one enzyme at a time. The new sensor gives engineers a way to connect intracellular cadaverine levels to a fast, sortable fluorescent signal. That makes it possible to evaluate pathway and genome-scale variation that would be impractical to assess through slower chemical measurements alone.
The reported strain reached 114.2 grams per liter of cadaverine, exceeding the previously cited E. coli titer of 84.1 grams per liter. The approach also offers a model for developing sensors when a target chemical lacks a dedicated natural regulator: mine the host's response to the chemical, identify a responsive promoter, then engineer it into a more useful screening tool. Future work will need to establish how broadly this design strategy transfers to other microbes and industrial metabolites.
Topics: Biosensors
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