Dr. Chen Haibin of Enzymaster: Empowering Synthetic Industry with Biocatalysis

Applications of synthetic biology are driving industrial synthesis toward a greener and smarter future.

As a vital branch of modern science, synthetic biology accelerates the development of new drugs and vaccines and promotes the production of sustainable biofuels and chemicals by redesigning and constructing biological components and systems. It also demonstrates significant potential in environmental protection, agricultural improvement, industrial biocatalysis, and the development of biosensors and diagnostic tools.

Recently, successfully held in Shanghai“The 1st CPHI Bio-Manufacturing Innovation and Development Conference in 2024”bringing together industry experts, entrepreneurs, and scientists from the global biomanufacturing sector to jointly discuss development trends, market opportunities, and challenges in biomanufacturing technology. Among them,Dr. Chen Haibin, Vice President and Co-founder of Enzymaster, delivered a keynote speech titled “Biocatalysis Empowering the Synthetic Industry,” sharing the outstanding performance of biocatalysis technology in pharmaceutical engineering, fine chemicals, and other fields, as well as Enzymaster’s innovative technological achievements.

Enzymaster, established in 2013, is a professional provider of comprehensive biocatalysis solutions, dedicated to the industrial application of enzymes in pharmaceutical engineering, fine chemicals, new materials, the bio-industry, energy conservation, and environmental protection. The company specializes in enzyme- and strain-related catalytic technologies. Its expert technical team possesses extensive experience in directed enzyme evolution, strain engineering, enzyme formulation, and the industrial-scale production of pharmaceutical intermediates and fine chemicals, making Enzymaster a professional and reliable partner in biocatalysis. Additionally, Enzymaster has independently developed the BioEngine enzyme development platform.^®, created and commercialized a series of original enzymes with independent intellectual property rights.

The following is a summary of the key points from Dr. Chen Haibin’s speech.

The history of the synthetic industry dates back to World War II, when Germany was forced to develop its own synthetic ammonia and urea technologies due to blockades. This historical event spurred the development of the modern synthetic industry and laid the foundation for today’s synthetic biology.

The industrial synthesis of compounds involves multiple steps, allowing us to observe the complete value chain and supply chain from basic raw materials to final products. This process begins with fundamental feedstocks such as coal, oil, natural gas, air, and water, which undergo a series of chemical transformations to ultimately yield various chemicals available on the market. Each link in the supply chain is critical—from raw material acquisition and intermediate production to the manufacturing of fine chemical products—until they reach consumers or industrial users. Every step influences the performance, quality, and cost of the final product.

Currently, the upstream market of the industrial synthesis sector is dominated by capital-intensive enterprises, with relatively concentrated raw material supplies and a transaction model primarily based on futures. Companies in this field typically need to possess strong capital strength and resource control capabilities. In contrast, technology-driven companies play a crucial role in the research and development (R&D) segment of the downstream market. This sector is highly competitive, with numerous participants ranging from thousands to tens of thousands. Such a market structure requires companies not only to continuously innovate technologically but also to adapt flexibly in their market strategies to meet rapidly changing market demands.

The field of synthetic biology is developing rapidly and faces intense market competition. Many companies are attempting to translate their innovative ideas into economic value. According to Dr. Chen, there are two development pathways for enterprises to stand out in the competition: one is to expand upstream by integrating the industrial chain, and the other is to develop downstream by establishing their own brands and sales channels.

Although the fine chemicals sector is crowded with participants and fiercely competitive, it actually offers abundant opportunities, making it a relatively accessible industry with significant potential. Existing data indicate that while human understanding of natural product compounds may not be as extensive as that of synthetically produced compounds, natural products have demonstrated unique importance in drug development, particularly in the production of antibiotics. Currently, approximately 500,000 natural product compounds have been identified, whereas the number of synthetic compounds is substantially larger, ranging from 8.8 million to 10 million. Although literature on natural products may be limited, these data are sufficiently representative to reveal the current state of compound discovery and synthesis, as well as the prospects for future research and industrial applications.

Furthermore, although millions of compounds have been identified and synthesized, this represents merely a drop in the ocean compared to the theoretical diversity of possible compounds. The number of compounds that could potentially be prepared within Earth’s environment is estimated to be as high as 10^60, yet humanity has explored and understood only an infinitesimal fraction of this vast chemical space. This indicates that there remains immense untapped potential for discovery and utilization in the field of compound research and development. Beyond existing products, the development of new products and novel applications highlights the substantial potential and promising prospects inherent in synthetic biology technologies.

Currently, the integration of synthetic biology with industrial synthesis has brought revolutionary changes to traditional synthetic processes.Biocatalysis is a significant innovation in the toolkit for compound synthesis. By leveraging enzymes evolved in nature and innovatively engineered by humans as catalysts, biocatalysis enables more efficient and environmentally friendly chemical reactions.This technology not only reduces production costs but also enables the development of new compounds and pharmaceuticals that are difficult to achieve through traditional chemical synthesis. Its applications have expanded from traditional fields such as food processing, detergents, and textiles to a broader range of chemical and pharmaceutical manufacturing sectors. With the continuous advancement of enzyme engineering and metabolic engineering, biocatalysis is poised to play an even greater role in future industrial synthesis.

As catalysts, enzymes are akin to hexagonal warriors in industrial production.Dr. Chen explained, “As catalysts, enzymes must not only efficiently catalyze specific chemical reactions but also exhibit high selectivity to ensure reaction specificity and efficiency. Stability is another critical attribute that enables enzymes to maintain their activity during continuous production processes. Furthermore, an enzyme’s resistance to inhibition by various compounds present during the reaction ensures its applicability in complex industrial environments. In commercial production, low-cost mass manufacturing and intellectual property rights are equally crucial, as they determine economic feasibility and market competitiveness.”

Currently, a vast number of enzymes in nature remain undiscovered or insufficiently studied. Advanced sequencing technologies enable the exploration of these uncharted territories to identify novel enzymes with potential industrial applications. As the cumulative number of artificially developed enzymes continues to grow, a substantial resource base has been established. Among industry players, Enzymaster has developed significant advantages in enzyme mining.

Typically, the discovery of enzymes begins with naturally evolved enzymes as a starting point. Enzyme mining can be conducted through bioinformatics; following molecular docking and virtual screening, gene synthesis is performed to evaluate the catalytic performance of the mined enzymes. Furthermore, for non-natural substrates or non-natural reactions, the enzyme mining process can be integrated with computational chemistry, involving quantum mechanics and molecular dynamics. This approach enables the identification of enzymes with basic catalytic activity through virtual screening, which are then engineered to better suit specific industrial processes. These methods not only broaden the industry’s understanding of enzymes but also provide greater possibilities for industrial applications.

Dr. Chen noted that translating enzymes from laboratory research to industrial applications requires careful consideration of their performance in actual production processes. This entails not only optimizing the enzymes themselves but also ensuring their compatibility with process workflows and production equipment. The co-development of enzymes and processes is an iterative endeavor, requiring continuous adjustment and optimization to achieve optimal production efficiency and cost-effectiveness.

As a high-tech enterprise dedicated to the fields of synthetic biology and enzyme engineering, Enzymaster focuses on developing novel enzymes and improving the performance of existing ones to serve industrial production and promote the development of green chemistry.

Over the course of nearly 11 years, Enzymaster has been dedicated to enzyme mining, engineering, and industrial-scale production centered on biocatalysis technologies, providing “end-to-end” comprehensive biocatalytic solutions from concept ideation to product commercialization.

Currently, Enzymaster has established two foundational technology platforms within the company—BioEngine^® Enzyme Directed Evolution Platform and BioNavigator^® Enzyme Virtual Technology PlatformBy leveraging biophysical energy calculations and bioinformatics analysis systems, Enzymaster achieves virtual computation and evolution in enzyme engineering. Combining wet-lab and dry-lab methodologies, the company continuously expands its diverse enzyme libraries and accumulates high-quality data, thereby accelerating commercialization. To date, Enzymaster has amassed extensive datasets, including enzyme data, small-molecule data, and reaction process monitoring data, while actively developing the EnzyAI artificial intelligence platform. In an era of increasingly mature AI technologies, these data assets have become invaluable.

Leveraging its two major technology platforms, Enzymaster has successfully commercialized 20 green biomanufacturing products, which are applied in industries such as pharmaceuticals, fine chemicals, and nutrition.These products incorporate Enzymaster’s globally original enzyme technology.To date, Enzymaster has filed over 60 patent applications, including 35 granted Chinese invention patents, many of which have also been pursued through international PCT patent applications. Currently, Enzymaster’s R&D service clientele includes the world’s Top 20 pharmaceutical companies and the global Top 10 fine chemical enterprises.

Although synthetic biology is currently a hot field, it still faces pain points such as the inability to fully implement innovative ideas. Dr. Chen provided a detailed demonstration of the entire process and key stages involved in the commercialization of biomanufacturing technologies.

As a cutting-edge technology, the implementation of biomanufacturing technology is divided into three key stages. First, in the "0→1" proof-of-concept stage, the focus is primarily on the design and optimization of synthetic routes, as well as the discovery and engineering of enzymes. During this phase, a diverse array of innovative technologies emerges, and researchers must ensure the feasibility of the synthetic pathways and the functionality of the enzymes.

Following proof of concept, the pilot-scale phase from “1→60” represents a major bottleneck that current biomanufacturing must address. At this stage, companies need to scale up the outcomes achieved during the proof-of-concept phase to ensure process stability and feasibility for mass production. In this process, enzyme engineering and manufacturing process optimization are not carried out in isolation; rather, they constitute a dynamic process of mutual influence and reinforcement. Continuously adjusting engineered enzymes and production processes is crucial to delivering qualified samples during the pilot-scale phase.

Having crossed the most critical threshold of pilot-scale testing, the stable mass-production phase of “60→100” poses a greater test to a company’s industrial capabilities. The goal at this stage is to achieve continuous and stable product manufacturing while ensuring that product quality meets established standards. Only by building robust facilities and supply chains to reliably support large-scale production can companies truly realize technological commercialization, transitioning from the laboratory to the factory and from 0 to 100.

Dr. Chen stated that during the product development process, initial concepts may need to be adjusted based on the practical realities of industrial applications. If an enzyme is already in industrial use and requires performance enhancement, this process is relatively straightforward. However, if it involves a completely new design pathway, more adjustments may be necessary to ensure the final product aligns with the original vision. “Enzymaster boasts a complete closed-loop system that allows customers and our team to dynamically adjust strategies to meet actual market demands, thereby facilitating technology commercialization and product delivery. This reflects our original intention and goal in entering the field of synthetic biology.”