CHEMICAL BIOTECHNOLOGY AND BIOCATALYSIS

The Chemical Biotechnology and Biocatalysis Division focuses on driving sustainable chemicals manufacturing and bioproducts development by integrating chemistry and biology that is enabled and accelerated by AI/ML and automation.

We concentrate on our efforts in two broad thematic areas:

• fine & specialty chemicals, fuels
• nucleotide chemicals & biomolecules

By exploiting synergistic hybrid chemical-biological catalysis methods, we create alternative, sustainable routes to chemicals from next generation feedstocks (e.g. CO2, waste plastics, biomass). Through these efforts, we aim to reduce reliance on fossil fuel feedstocks, re-invent manufacturing pipelines, advance Singapore’s Energy & Chemicals sector transformation, and support our nation’s NetZero ambitions to transition to a green and low-carbon economy.

• Biocatalyst Design & Engineering: Our data-driven biocatalyst platform features integrated chemistry, analytics, custom high throughput assays and biocatalyst engineering/immobilization capabilities accelerated by AI/ML-driven workflows to develop efficient, robust biocatalysts for industrial applications.
• Chemoenzymatic Route Development: Leveraging our chemistry and biology expertise synergistically, we develop hybrid chemical-biological catalysis routes to sustainably manufacture high-value specialty chemicals such as nucleotide triphosphates (NTPs), agrochemicals, and pharmaceuticals.
• Next Generation Feedstock Valorisation: We investigate frontier chemical-biological catalysis methods to transform CO₂, biomass, or waste plastics into valuable chemicals (e.g. C6 chemicals), as part of the efforts towards waste reduction and circular economy.
• Multi-Modal Informatics: We develop high throughput informatic tools to accelerate the curation and exploration of large datasets. We also pioneer multi-modal informatic systems equipped with AI algorithms to connect disparate chemical and biological datasets, enabling accelerated discovery and innovation in sustainable chemical manufacturing.

By integrating sequence mining, biocatalyst engineering, and generative protein language models (PLMs), we have designed biocatalysts with enhanced efficiency and stability compared to the state of the art, enabling the breakdown of polyethylene terephthalate (PET) plastic into its original monomers under mild, environmentally friendly conditions. This innovation not only offers a greener alternative to traditional recycling methods but also contributes to a circular economy by facilitating the upcycling of plastic waste into valuable resources. For a highlight of one of our works, please see: https://research.a-star.edu.sg/articles/highlights/natures-solution-to-plastic-pollution/

To address the bottlenecks of conventional enzyme development, we (together with collaborators from A*STAR BII and SIFBI) established an integrated computational-experimental workflow that significantly streamlines the optimization process by minimizing the need for extensive trial-and-error experimentation. Applied to galactose oxidase (GOase), this approach demonstrated a 100- to 150-fold acceleration in development speed, enabling rapid tailoring of enzyme properties such as stability, solubility, and catalytic activity for industrial applications. These engineered enzymes facilitate the production of specialty chemicals (e.g. pharmaceuticals) under mild, environmentally friendly conditions, reducing reliance on harsh chemicals and energy-intensive processes. For a highlight of one of our works, please see: https://research.a-star.edu.sg/articles/highlights/evolving-enzymes-for-greener-goods/

We partner with A*STAR SIFBI, NUS and Mojia Biotech to pioneer the production of bio-based molecules that are cost-competitive and serve the needs of various industries. Leveraging on our enzyme engineering platform and Mojia’s Cn+Bio^TM biopathway, we are developing the next generation route to 1,3-propanediol (PDO), a key ingredient for a broad array of industries such as skincare products, coatings and biodegradable plastics. For more details please see: https://www.a-star.edu.sg/News/astarNews/news/press-releases/mojiabio-astar-sustainable-biomanufacturing-platform

We pioneer powerful new approaches to explore Nature’s chemical potential by integrating protein language models (PLMs) and molecular language processing through integrated chem-bio-informatics to uncover microbial producers of specialty chemicals and bioactives at unprecedented speed and scale. Such an approach is only made possible through our in-house developed informatics platforms, including tools that enable direct structural elucidation of compounds from complex biological mixtures—without relying on traditional experimental reference libraries. Coupled with genomic data, our integrated analysis is drastically reducing time and resources needed to identify to sustainable solutions in specialty chemical manufacturing. For an example of one of our works, please see: https://research.a-star.edu.sg/articles/highlights/millions-of-natures-secrets-revealed/

Traditional chemical synthesis of nucleoside triphosphates (NTPs), which are building blocks for mRNA, is complex, environmentally hazardous, and relies on toxic reagents. Our team has developed a chemoenzymatic process that uses a tailored cocktail of enzymes to convert nucleosides into natural and non-natural NTPs, such as pseudouridine triphosphate and N1-methylpseudouridine triphosphate that are critical for mRNA development. By replacing tedious chemical processes with chemoenzymatic routes, we are making this key raw material production safer, greener, and more scalable, thus paving the way for faster and more sustainable mRNA development. For an example of one of our earlier works, please see: https://pubs.rsc.org/en/content/articlehtml/2023/re/d2re00381c