Matthew Chang The Bioeconomy, Reengineered

13 Oct 2025

The Bioeconomy, Reengineered

by Prof Matthew Chang with Asst Prof Lee Jungjoon, Assoc Prof Poh Chueh Loo, Assoc Prof Li Zhi, and Dr. Ang Hui Ying

Director, Singapore Consortium for Synthetic Biology (SINERGY) | Director, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI) | Director, Wilmar and NUS Corporate Laboratory (WIL@NUS) | NUS Medicine

Ignite Issue 02

13 Oct 2025

The Bioeconomy, Reengineered

by Prof Matthew Chang with Asst Prof Lee Jungjoon, Assoc Prof Poh Chueh Loo, Assoc Prof Li Zhi, and Dr. Ang Hui Ying

Professor Matthew Chang

It has been 30 years since the first bacterial genome was sequenced. A decade later came a complete map of the approximately 25,000 genes, non-coding regions, regulatory regions and structural sequences of DNA that make up the human genome. Today, tens of thousands of bacterial strains and thousands of animal species have had their genomes sequenced.

These genetic blueprints tell highly complex stories. When learning a language, knowing how to spell a word can only get you so far in communicating information. It is also crucial to understand how words relate to each other in various contexts. Likewise, it is crucial to comprehend the relationships between various genome elements within the context of genome regulation and protein function.

Understanding this genetic code unlocks the ability, with the right tools, to manipulate it in ways that instil new functionalities in cells or mitigate the consequences of genomic abnormalities. This is the fundamental premise of engineering biology, or synthetic biology, an emerging field that aims to design and engineer novel biological systems and is poised to revolutionise how fine chemicals are manufactured, how metals are recovered from electronic waste, and how personalised therapeutics are administered.

Precision Genomic Engineering

One tool that propelled the field forward over the past decade is CRISPR-Cas9, a gene editing method that allows researchers to efficiently cut DNA in living organisms at specific sites, to remove or disrupt genes, or even insert new genes. It is one of the most revolutionary gene editing methods currently in use. Today, the technology continues to evolve. Scientists can now make DNA substitutions using ‘base-editors’, and DNA insertion, deletion and substitutions using ‘prime-editors’. Mitochondrial and chloroplast DNAs can also be targeted for editing.

Assistant Professor Jungjoon Lee leads the Genome Re-Innovation Lab under the NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI). His work focuses on developing and optimising gene editing tools and assays to ensure CRISPR safety. His team developed a directed evolution system called Sniper-screen, an Escherichia coli (E. coli)-based screening system designed to select optimised Cas9 variants with high activity and specificity. They demonstrated that Sniper2L, their latest product, possesses these features through high-throughput screens and small molecule assays. Additionally, his team developed Extru-seq and TAPE-seq, genome-wide off-target detection methods for Cas9 and Prime Editor.

"The field has reached a tipping point, and we will continue to hear news about the approval of new drugs and foods produced from edited genomes. In both fields, people are very sensitive to safety issues. Our lab is committed to developing optimised versions of CRISPRs and safety assays to address these concerns"

Enter AI

While many new technologies are changing how genomes are designed and deployed, there is one that stands above the rest for its potential to be the next revolution in the field – artificial intelligence.

Identifying the elements required to produce a viable, bioengineered system, becomes a seemingly insurmountable task when considering the vast number of biomolecular interactions that are at play to maintain genome regulation and cellular function. Traditionally, a ‘trial-and-error’ approach was the go-to method, however today, AI-based tools are opening new avenues to better design, grow and utilise bioengineered genomes.

They can, for example, analyse complex datasets, identifying functional elements, and predicting outcomes with greater accuracy. AI-driven platforms like DeepCRISPR enhance genome editing efficiency, while AlphaFold accelerates protein structure prediction. Computer-aided design and modelling tools like Cello, Cameo, OptKnock accelerate the design and engineering of microbes by optimising gene circuits, metabolic pathways and strain performance. Tools like these promise increased capabilities and efficiency in guiding synthetic genome design and construction.

Just as electrical engineers use software to design integrated circuits, synthetic biologists use computer-aided design and modelling tools, as well as AI models, to design genetic circuits – combinations of genes that control specific cellular behaviours, and predict how genetic circuits will behave in living cells.

At the Engineering Biology Lab within NUS SynCTI, for example, Associate Professor Chueh Loo Poh, and his team apply engineering principles to design and construct microbes with specific capabilities. To accelerate the process, they developed foundational modelling tools such as BioModel Selection System (BMSS2) – a unified platform to streamline and automate gene circuit model selection, enhancing efficiency in gene circuit design. To harness the powerful capability of AI, the team integrates machine learning with ultra-high throughput sorting technology for large-scale sequence-function data generation and screening. This synergy enables the discovery and design of novel high-performance enzyme sequences, revolutionising enzyme engineering by coupling experimental precision with AI-driven predictive design.

Tools are also now being developed to predict promoter strength and protein structure from genome sequences, predict function from molecular structure information, aid the directed evolution of proteins, forecast base editing outcomes, accelerate metabolic pathway design and optimisation, and streamline analytical chemistry data processing during the test step of strain engineering.

A key driver in tomorrow’s bioeconomy

As the engineering biology toolkit expands – with new genome engineering technologies, synthetic biology platforms, and advanced computational methods – and as the network of domain experts grows, innovation and discovery will naturally accelerate. This convergence of expertise and cutting-edge tools is driving a transformation across industries, introducing new methods for developing and deploying products and processes. Healthcare, agriculture, biomanufacturing, and sustainability are just some areas already benefitting from these advances.

Collectively, these changes are laying the foundation for a robust future bioeconomy, where biology is harnessed to address global challenges and drive economic growth.

To date, the pace of translating engineering biology research into market-ready products has been relatively fast. Typically, bio-based startups must navigate lengthy preclinical testing, extended clinical trials, and a complex regulatory approval process. These ventures also demand substantial, high-risk financial investments, placing investors in a challenging position due to the inherent uncertainty of scientific research. Furthermore, many technologies that could eventually address critical issues such as stability, scalability, and efficient production are still in development and may not yet exist.

Nevertheless, the field has achieved notable milestones. Today, several Nasdaq-listed companies are focused on genome editing techniques, and the FDA has approved the first CRISPR-based human therapeutics.

In 2024, CRISPR-edited food products began to enter the US market, marking a milestone in agricultural biotechnology. Additionally, laboratory advances have enabled microbes to sustainably produce key components for lab-grown meats, bio-based plastics, and advanced biofuels. As one example, NUS SynCTI has successfully developed specialty chemicals in collaboration with industry partners, including Wilmar International and HH Chemical, highlighting the rapid progress and broad impact of engineering biology.

Despite early progress, the full potential of engineering biology still faces important challenges before it can be fully realised. One key consideration is how products developed through biologically engineered systems are perceived by the public. Building trust through transparency and clear communication will be essential throughout the development process. Creating opportunities for open dialogue and increasing public familiarity with these innovations can help foster broader acceptance and confidence in both the products and the technologies behind them.

Consistent regulatory standards are equally critical. Fragmented regulatory frameworks can hinder the scalability and international trade of bio-based products. Globally recognised standards and metrics are essential to support the safe, efficient, and timely adoption of biologically engineered systems and their applications.

In response to this need, the Task Force on Engineering Biology Metrics and Technical Standards for the Global Bioeconomy¹ was established in 2024. Professor Matthew Chang, Director of NUS SynCTI, is a member of this international task force.

“We have identified 10 critical areas – six technical and four non-technical – where the development of standards and metrics is essential to unlock the full potential of the bioeconomy,” he said.

“The rapid pace of advancement in biotechnology often outpaces regulatory and policy updates, creating uncertainty for innovators. That’s why ongoing communication and transparency between researchers, regulators, and the public are critical. These conversations help ensure that policy decisions are informed by the latest scientific understanding.”

To further accelerate bioeconomic growth, sustained public investment in research and innovation remains essential. NUS recently launched a S$120 million national research initiative to harness engineering biology for the sustainable production of chemicals vital to energy, materials, consumer products, and nutrition. This initiative focuses on developing next-generation engineering biology platforms for sustainable biomanufacturing from renewable feedstocks, including carbon dioxide.

At the national level, Singapore’s Green Plan 2030 is pursuing a steadfast commitment to sustainability and fostering a supportive environment for industries to pursue bio-based solutions.

Engineering biology stands at the forefront of a new era and is poised to revolutionise how we produce, consume, and sustain. From addressing climate change and food security to advancing resource efficiency, the field offers transformative solutions to some of humanity’s most urgent challenges. Realising this potential will require bold investment, adaptive regulatory frameworks, and cross-border collaboration.

With its integrated approach to innovation, policy, and public engagement, Singapore is rapidly emerging as a global leader in engineering biology. As part of this national effort, NUS is advancing cutting-edge research, shaping global standards, and developing next-generation technologies in engineering biology, contributing to a more resilient, inclusive, and sustainable future.

References

Freemont, P.S., Ni, C., Aurand, E., Chang, M.W., Hook-Barnard, I., Malley, J., Romantseva, E., Strychalski, E., Vavitsas, K. 2024. Engineering Biology Metrics and Technical Standards for the Global Bioeconomy. London, UK. https://doi.org/10.25561/110822

This article was first published in Ignite Magazine, Issue 02.

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