NUS researchers achieve breakthrough in engineering colour-sensing yeast

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Aug 11, 2026, 05:56 ET

In a new study, scientists engineered baker's yeast to sense and respond to different colours of light, enabling new ways to control cellular behaviour with red and blue light

SINGAPORE, Aug. 11, 2026 /PRNewswire/ -- Baker's yeast is one of biotechnology's most important microorganisms. It has long been used to leaven bread and ferment beer. More recently, advances in synthetic biology have enabled engineered yeast to convert sugar into a wide range of products, including medicines, fuels and industrial chemicals.

Yet even well-engineered yeast cells can be difficult to control in a precise and timely way. A team of researchers from the National University of Singapore (NUS), led by Associate Professor POH Chueh-Loo from NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) and Department of Biomedical Engineering under the College of Design and Engineering (CDE) at NUS, addressed this challenge using optogenetics, a strategy that rewires cells so that selected genes turn on or off in response to light. By exposing yeast to different colours and patterns of light, the team showed that biological instructions could be delivered dynamically, without repeatedly adding chemical inducers.

"Achieving precise, dynamic control over cellular machinery has been a goal in synthetic biology," explained Assoc Prof Poh. "By using different colours of light to dictate complex, multi-step processes, we are paving the way to make biological manufacturing more predictable and programmable."

While yeast has been previously engineered to respond to single colours of light, this is the first time that a single strain of yeast has been engineered to respond to more than one colour.

The NUS team published their research findings in the scientific journal Nature Communications on 22 May 2026.

Life in Technicolour

A key challenge was to make yeast respond reliably to red light. Existing red light-responsive optogenetic systems in yeast require several introduced genes, additional cofactors (or "helper" molecules) or careful handling to avoid unintended activation. These limitations make them difficult to combine with other light-controlled systems.

The team adapted a light-sensitive tool previously used in bacteria and mammalian cells into a single red light-responsive protein for yeast, which they named y-iLight. When exposed to red light, y-iLight attaches to certain DNA sequence in the yeast and turns on specific genes. Importantly, y-iLight works without the need for additional chemicals beyond those naturally found in yeast, making it simpler, more cost-effective, and more reliable for practical use.

Engineering yeast to see red and blue

Although y-iLight was an important improvement, it initially had a serious limitation: blue light could also activate it. This crosstalk meant that the red light system could not yet operate independently alongside a blue light system.

To solve this, the researchers used a modular protein-engineering strategy. They fused y-iLight to protein modules designed to block its activity specifically under blue light, then tested different combinations to identify variants that preserved red light responsiveness while suppressing unwanted blue light activation.

When the improved red light system was combined with the established blue light-responsive system called EL222, the researchers achieved independent control of two gene-expression channels in the same yeast strain. This represents a major step toward multiplexed optogenetics in yeast.

"Achieving this level of independent control without the two systems interfering with each other was a major hurdle in yeast," says Linus TAN Yu-Han, PhD student at NUS CDE and lead author of the paper. "By solving the blue-light crosstalk issue, we opened the door to much more complex genetic programming in yeast using colour."

Colourful instructions for cell factories

With a dual-channel optogenetic yeast strain in hand, the team demonstrated how multi-coloured light could deliver more complex instructions. They placed two enzymes involved in producing luteolin, a natural plant chemical with potential health-related applications, under separate red and blue light control. By exposing the yeast to different proportion and timing of red and blue light, the researchers could adjust how the yeast made luteolin.

This light-based control also helped researchers understand how the process worked. In particular, they discovered that one enzyme, called F3′H, was less effective in the later stages of culture, providing useful insight on how to improve the process in the future.

The team also used optogenetics to control how yeast cells behave. By linking the flocculation gene FLO1 (which makes yeast cells stick together) to a red light-activated genetic switch, they showed that red light could trigger yeast cells to clump together and sink.

In their experiment, yeast first produced luteolin under blue light, then clumped together under red light. This demonstrates how light can control production and separation, which could inspire cleaner and more programmable biomanufacturing strategies.

Paint me a picture

Optogenetics also offers spatial control: genes can be switched on only where light is projected. To demonstrate this, the NUS team engineered yeast to produce different coloured compounds in response to red or blue light, spread the cells as a thin layer on agar, and projected light through masks. The result was a set of patterned, multi-colour "living images" grown by yeast.

"Together, the work shows that yeast can be programmed with multiple colours of light to control gene expression, metabolic pathways, cell behaviour and spatial patterning. The platform could support future applications in biomanufacturing, pathway optimisation and living materials," Assoc Prof Poh explained.

What's brewing next?

Assoc Prof Poh and his lab are currently working on ways to use rationally designed gene networks to boost the properties of these light sensitive proteins. With increased strength and sensitivity, they believe it will create new opportunities in the way microbes are used to manufacture valuable chemicals and materials.

SOURCE National University of Singapore