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Prof. Anping Zeng: Can You Live with Just Breathing the Air? Synthetic Biology Can Do More

26, 2022

Email: zhangchi@westlake.edu.cn
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On April 26, 2021, Prof. Anping Zeng, then a tenured professor at the Hamburg University of Technology and director of the Institute of Bioprocess and Biosystems Engineering, had a dream - using air, water, and lightning for biosynthesis to produce chemicals and proteins, and all kinds of things we want.

This is a very grand vision, but not just a distant dream for humankind.

Zeng is an internationally renowned expert in the field of synthetic biology and a member of the German Academy of Engineering. In the spring of 2022, he joined Westlake University full-time as a chair professor of synthetic biology and bioengineering, and as the director of the Center for Synthetic Biology and Biological Intelligence at Westlake University.

To understand Zeng’s work, we must first know what synthetic biology is. Synthetic biology is the use of engineered microorganisms and cells (such as various bacterial and animal cells), as well as cellular components (such as RNA and proteins), to produce various substances required by humans, or generate completely new biomolecules and organisms for medical diagnosis, protection and clinical treatment. Synthetic biology is listed as a frontier research direction of science and technology in China's "14th Five-Year Plan", and it is also praised by the US Department of Defense as one of, "six disruptive basic research areas to focus on in the future".

In terms of biomanufacturing, synthetic biology can realize the biosynthesis of more than 60% of important chemicals, fuels, natural products and raw materials. However, less than 6% of chemicals have been biomanufactured. According to McKinsey's 2021 forecast, in the next 10-20 years, biomanufacturing will represent a trillion-dollar market annually.

A series of studies on the biosynthesis of diols, especially 1,3-propanediol, is representative of Zeng’s past work. 1,3-Propanediol is an important organic chemical and raw material mainly used in a new generation of chemical fibers, inks, coatings, cosmetics, pharmaceuticals and other industries, and it is relatively environmentally friendly. Its bioprocess production is also a benchmark achievement in industrial biotechnology over the past two decades. It is a pity that the technology of producing 1,3-propanediol by biological fermentation was monopolized by DuPont in the United States in the past. Zeng’s team developed a new strain of Clostridium pasteurii and a number of innovative process technologies to efficiently produce 1,3-propanediol. Enlarging the project and carrying out large-scale industrial application development in China in order to break the monopoly of DuPont.

Zeng said, "Microbes have temperaments and personalities. Engineering biology is to domesticate and transform it to mass-produce whatever we want." Completing this process requires a tight integration of science and engineering. This is also the core idea of synthetic biology and its technology.

In recent years, the most famous example of synthetic biology is the technology of carbon dioxide artificial starch synthesis. In layman's terms, in the future, humans may be able to eat enough by "drinking the northwest wind", to use an old Chinese expression. This technology has enormous implications for food security, extra- terrestrial exploration, and climate change.

This year, Chinese scientists achieved the world's first de novo synthesis of carbon dioxide into starch in the laboratory. Zeng said of the achievement, "this is a very beautiful work in biosynthesis." Though a vision of living with just breathing the air is still a long way off.

The air is mainly composed of nitrogen and oxygen. The carbon dioxide content in the air is only about 0.03%. It is a very big technical challenge to really use such a thin concentration of carbon dioxide to synthesize. But if the carbon dioxide in the air can be used as a raw material, the problem of carbon neutrality can be really solved. This is also an important field that Zeng hopes to cultivate in the future at Westlake University - fifth generation (5G) bio-manufacturing technology.

"Generally speaking, we use starch and sugar as raw materials, and use traditional methods to transform strains, which is called first-generation biotechnology, second-generation biotechnology uses genetic engineering to transform strains, and the third- generation uses algal microorganisms, carbon dioxide and light. Energy biosynthesis and refining technology, these three generations have a common feature, basically using a single microorganism to complete. Now a trend is to use a multi-enzyme or multi- microorganism mixed system to complete the bio- manufacturing process. If this is the fourth generation of biotechnology, then what we are doing now is beyond the third generation, and even beyond the fourth generation of 5G biomanufacturing.”

This means work in two directions, the first is to achieve basic biosynthesis from substances present in the sky such as air, water, lightning. The second aspect is to combine basic biosynthesis with large-scale biomanufacturing technology for industrialization to achieve sustainability of raw material cost and supply.

At present, the research of Zeng’s team at Westlake University is closely related to the core scientific issue of the regulation mechanisms of the 1-carbon to 3-carbon metabolic system and its engineering application. "Carbon dioxide is a 1-carbon compound, glycine is a 2-carbon compound, and pyruvate has 3 carbons, 1 to 2, 2 to 3, just like three things, from the perspective of biosynthesis, there are single carbons such as pyruvic acid, but you can make anything,” Zeng said.

In its research, Zeng’s team has achieved some good results. For example, they have opened up the biosynthesis of 1-carbon to 3-carbon. In addition, the team discovered for the first time that one of the enzyme proteins has a reversible phase transition function and can form a single-component active hydrogel. This discovery gave birth to a new field of research - synthetic biology of catalytically intelligent soft matter. This will play a new role in artificial meat, 3D cell culture, biological tissue/ organ 3D printing, and other future industries.

At the same time, this discovery can also promote the research progress of biosynthesis using carbon dioxide in the air. For example, why can plants “drink the northwest wind?” It is because of the unique soft matter catalytic system that Zeng’s team will continue to study.

China attaches great importance to the emerging disciplines of "carbon neutrality" and synthetic biology. If the basic scientific research and engineering technology of synthetic biology can be combined, it is possible to truly realize source innovation and make significant bioengineering and engineering breakthroughs. This is also the original intention of Zeng when he returned to China to come to Westlake University. He hopes to cooperate with other excellent teams here at the Center for Synthetic Biology and Bio-Intelligent Manufacturing (WE-SynBio) of Westlake University to develop a truly carbon-neutral Westlake solution.

Zeng believes that the future belongs to atmospheric (5G) biosynthesis. As Hegel once said, "A nation has some people who pay attention to the sky, and they have hope."