The work, led by Associate Professor Poh Chueh Loo of NUS Synthetic Biology for Clinical and Technological Innovation and the Department of Biomedical Engineering, addresses a longstanding problem in synthetic biology: how to control engineered cells precisely without repeatedly adding chemical inducers. Although yeast can be redesigned to manufacture medicines, fuels, industrial chemicals and other valuable compounds, biological production systems are often difficult to start, stop or coordinate at the right moment. Light offers a cleaner and more responsive alternative because it can be delivered rapidly, withdrawn instantly and projected onto selected regions.

The researchers used optogenetics, a technique that connects light-sensitive proteins to genetic switches. When activated by a particular wavelength, these proteins interact with DNA or with other regulatory components, changing the expression of selected genes. Earlier studies had produced yeast systems responsive to individual colours, but a single strain able to interpret multiple colours independently had not previously been demonstrated. The NUS team’s system creates two separate communication channels: red light controls one set of genes, while blue light controls another.

A central part of the study was the development of y-iLight, a compact red-light-responsive protein adapted from a tool previously used in bacteria and mammalian cells. In yeast, y-iLight binds to specific DNA sequences after exposure to red light, activating nearby genes. Unlike several earlier red-light systems, it does not require additional cofactors or helper chemicals beyond molecules naturally present in yeast. That simpler architecture could make the system easier to combine with other genetic circuits and more practical for industrial or laboratory applications.

The first version of y-iLight, however, had a serious weakness: blue light could also activate it. This unwanted response, known as crosstalk, would make it impossible to use red and blue signals as independent instructions. The researchers addressed the problem through modular protein engineering. They attached y-iLight to regulatory modules designed to suppress its activity specifically in the presence of blue light, then screened combinations of these modules to identify variants that retained strong red-light activation while reducing accidental responses to blue illumination.

The improved red-light switch was paired with EL222, an established blue-light-responsive system. In the resulting yeast strain, red and blue light could activate different genes without substantial interference between the two channels. This dual-colour control allowed the researchers to test more sophisticated genetic programmes in which distinct biological steps could be triggered separately, in sequence or simultaneously. Such multiplexed optogenetics could provide a more precise way to manage engineered pathways than chemical induction, which often affects an entire culture at once and can be difficult to fine-tune.

To demonstrate the system’s potential in biomanufacturing, the team placed two enzymes involved in the production of luteolin under separate light controls. Luteolin is a naturally occurring plant compound being investigated for potential health-related applications. By adjusting the proportions and timing of red and blue light, the researchers changed how the yeast directed its metabolic resources toward the compound. The experiments also revealed that one enzyme, F3′H, became less effective during later stages of culture, offering a clue that could help researchers improve the pathway’s performance.

The light-responsive yeast was also programmed to change its physical behaviour. The researchers linked the flocculation gene FLO1 to the red-light switch. FLO1 produces a protein that promotes adhesion between yeast cells, causing them to form clumps and settle. In one demonstration, the cells first produced luteolin under blue light and were then exposed to red light, which triggered aggregation. The sequence combined production and separation in a single biological process, suggesting a possible route toward more efficient and less chemically intensive manufacturing.

The system can respond not only to colour and timing but also to location. To show this spatial capability, the team engineered yeast to produce differently coloured compounds in response to red or blue light. The cells were spread as a thin layer on agar, and masks were used to project selected patterns onto them. As the illuminated regions activated different genetic programmes, the yeast grew into patterned, multicoloured “living images.” While the display is primarily a demonstration, the experiment highlights how optogenetic microbes could one day contribute to living materials, biological sensors or spatially organised manufacturing.

The researchers say stronger and more sensitive light-responsive proteins could expand the technology’s usefulness. Future work will focus on rationally designed gene networks that improve the performance of the switches and enable increasingly complex instructions. By combining multiple wavelengths with programmed exposure schedules and precise illumination patterns, scientists may be able to coordinate entire metabolic pathways or cellular behaviours in real time. The study, published in Nature Communications on 22 May 2026, marks a step toward yeast that functions less like a passive production vessel and more like a programmable biological machine.

Subject of Research: Experimental study of engineered yeast, optogenetics, gene expression, metabolic pathways and cellular behaviour.

Article Title: Dual-channel optogenetics in yeast for multiplexed light-based control of cellular processes and pathways

News Publication Date: 22 May 2026

Web References: National University of Singapore: https://www.nus.edu.sg/ ; NUS Synthetic Biology for Clinical and Technological Innovation: https://syncti.org/ ; NUS Department of Biomedical Engineering: https://cde.nus.edu.sg/bme/

References: Nature Communications, DOI: 10.1038/s41467-026-73399-0

Image Credits: National University of Singapore

Keywords: optogenetics, baker’s yeast, synthetic biology, red light, blue light, y-iLight, EL222, gene expression, metabolic engineering, luteolin, FLO1, biomanufacturing, living materials, National University of Singapore

Monovalent protein G represents a significant advancement over traditional bivalent versions due to its unique binding characteristics. By focusing exclusively on the Fc region of antibodies, the engineered protein enhances binding affinity and specificity without the complications associated with bivalency. In the past, achieving precise control over affinity purification processes presented numerous challenges, often resulting in suboptimal yields or co-purification of non-target substances. Mayrhofer and Skerra’s innovative approach effectively addresses these challenges, demonstrating clear advantages in both efficiency and specificity.

One of the key features of this engineered protein is its light-activated mechanism. This advancement aligns with the growing trend towards utilizing optogenetics in biological applications. By incorporating light-responsive elements, the researchers designed a protein that can be activated or deactivated with the introduction of specific wavelengths of light. This allows for precise control over the binding process in real time, enabling scientists to perform purifications with unprecedented accuracy while reducing the risk of cross-reactivity or contamination that often accompanies traditional methods.

The engineering of this monovalent protein G involved complex molecular modifications to enhance its properties. Researchers employed cutting-edge techniques such as site-directed mutagenesis and phage display technology to create variants with optimized binding affinities. The resulting protein constructs exhibited exceptional stability and specificity towards various antibody isotypes, which is critical in diverse experimental contexts. This focused engineering approach emphasizes the intrinsic versatility of protein design, demonstrating how targeted modifications can yield significant improvements in functionality.

The ability to switch on and off the binding activity using light opens up new avenues for the real-time monitoring of biological processes. In laboratory settings, this capability allows researchers to adapt purification conditions dynamically, potentially leading to enhanced yields and purity levels. Such advancements could substantially improve the production processes for therapeutic antibodies, which are highly valuable in treating a range of diseases, from autoimmune disorders to cancer.

Moreover, the engineered monovalent protein G could play a pivotal role in the development of antibody-based diagnostics. By allowing for precise and selective antibody isolation under controlled conditions, it could facilitate the creation of highly accurate diagnostic tests. This is particularly relevant in the context of rapidly evolving infectious diseases, where timely and reliable diagnostic solutions are critical.

As these researchers continue to unveil the intricacies of their engineered protein, it becomes evident that the implications of this work extend well beyond the laboratory bench. The commercial potential for such innovations is immense, particularly within the biopharmaceutical industry, which relies heavily on antibody production for therapeutic purposes. Companies may soon leverage these advancements to enhance their manufacturing processes, resulting in more cost-effective and efficient production methods.

Furthermore, the methodology presented in this study serves as a blueprint for future protein engineering endeavors. Researchers can draw upon these principles to create other monovalent proteins tailored for novel applications or enhanced specificity. As the demand for customized proteins increases, such engineering strategies will likely gain prominence across multiple disciplines, including biotechnology, synthetic biology, and drug development.

This breakthrough also aligns with the broader trend of integrating green chemistry principles into laboratory practices. By utilizing light as a control mechanism, the protein purification process may reduce the need for harmful chemical reagents, making it more environmentally friendly. Such considerations are increasingly essential in today’s scientific community, where sustainability is placing a significant emphasis on environmental impact.

In conclusion, the innovation presented by Mayrhofer and Skerra heralds a new era in the field of protein engineering and antibody purification. By developing a light-controlled, monovalent protein G specifically targeting the Fc region of antibodies, they have not only advanced our understanding of affinity purification but have also opened doors to novel applications and methods in biotechnology. The future of antibody purification is bright, with this pioneering research paving the way for more efficient and environmentally considerate approaches to biotechnology.

As additional studies explore the efficacy of this engineered protein in various settings, it may soon become a staple in laboratories worldwide, revolutionizing how researchers interact with and utilize antibodies. The anticipated impact of these advancements underscores the importance of ongoing research in protein design and purification, highlighting the limitless opportunities that lie ahead.

Given the potential for optimized antibody production, enhanced diagnostic accuracy, and the integration of sustainable practices, it is clear that the work of Philipp Mayrhofer and Andreas Skerra represents a significant leap forward in biotechnological applications. This research not only marks an accomplishment in protein engineering but also exemplifies the continuous evolution of methodologies that are set to define the future of scientific progress.

In summary, the engineering of an Fc-specific monovalent protein G is not just an innovation but rather a pivotal milestone in enhancing the methods of antibody purification and production. Its implications stretch across therapeutic and diagnostic domains, promising to reshape the landscapes of these critical fields. As we reflect on this remarkable development, it is impossible not to be excited by the future possibilities it holds for biotechnology.

Subject of Research: Engineering of an Fc-specific monovalent protein G for antibody purification.

Article Title: Engineering of an Fc-specific monovalent protein G for the light-controlled affinity purification of antibodies.

Article References: Mayrhofer, P., Skerra, A. Engineering of an Fc-specific monovalent protein G for the light-controlled affinity purification of antibodies.
Sci Rep 15, 38111 (2025). https://doi.org/10.1038/s41598-025-25894-5

Image Credits: AI Generated

DOI: 10.1038/s41598-025-25894-5

Keywords: Protein Engineering, Antibody Purification, Light-Controlled Mechanisms, Biopharmaceuticals, Monovalent Protein G.