Researchers at the National University of Singapore (NUS) have achieved a milestone in synthetic biology by engineering a strain of baker's yeast (Saccharomyces cerevisiae) capable of responding independently to multiple colours of light.
Led by Associate Professor Poh Chueh-Loo from NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) and the Department of Biomedical Engineering, the team utilised optogenetics to control gene expression dynamically. By exposing the yeast to red and blue light patterns, the researchers controlled complex multi-step biological processes without relying on repeated chemical inducers.
Published in Nature Communications, the research provides a foundation for programmable biomanufacturing, offering enhanced control over the production of high-value bio-based ingredients, speciality chemicals, and pharmaceuticals.
Dual Channel Optogenetic Control in Synthetic Biology
While yeast has previously been engineered to respond to single wavelengths of light, achieving independent control across multiple channels within a single strain has historically presented technical hurdles due to optical crosstalk.
To address this, the NUS team engineered a red light-responsive protein system named y-iLight. Adapted from bacterial and mammalian optogenetic tools, y-iLight binds to target DNA sequences under red light to activate specific genes without requiring additional chemical cofactors.
To eliminate blue light cross-activation, the researchers engineered y-iLight with blocking protein modules. When combined with the established blue light-responsive system EL222, the dual-channel framework allowed independent control over two distinct gene expression pathways in the same cell line.
Industrial Bioprocessing and Fermentation Applications
The team demonstrated the practical utility of the colour-sensing yeast across both metabolic pathway regulation and cellular behaviour management.
Key technical specifications and functional achievements include:
đŽ y-iLight System: Red light-activated protein engineered to operate natively in yeast without supplementary helper molecules.
đ” Crosstalk Suppression:Â Modular protein engineering eliminated blue light interference, securing independent dual-channel genetic control.
đż Pathway Fine-Tuning:Â Regulated the production of luteolin, a natural plant compound, by adjusting the timing and proportions of red and blue light exposure.
𧫠Automated Cell Separation: Linked the flocculation gene $FLO1$ to red light activation, enabling light-triggered cell clumping and settling to simplify post-fermentation separation.
During testing, the yeast produced luteolin under blue light before switching to red light to trigger cell aggregation and clarification. This integration of production and separation mechanisms highlights the potential for cleaner, less resource-intensive downstream processing in industrial fermentation.
Future Trajectory for Bio-Based Manufacturing
The study also revealed insights into metabolic bottlenecks, such as identifying late-stage efficiency limits in the $F3'H$ enzyme during luteolin synthesis. These data points provide actionable targets for further genetic optimisation.
Associate Professor Poh Chueh-Loo noted that the platform demonstrates how multi-coloured light can program gene expression, metabolic output, and physical cell behaviour simultaneously.
The NUS research team is currently developing rationally designed gene networks to enhance the sensitivity and performance of these light-sensitive proteins, aiming to scale the technology for broader industrial biomanufacturing applications.
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