In March 2023, the US government announced an ambitious new course for its national bio strategy. It’s aptly named “Bold Goals for U.S. Biotechnology and Biomanufacturing” with key targets on:
Insider
Dr. Min Zhou is the CEO of CM Venture Capital, a China-based investment company which partners multinationals to help them invest in next-gen technologies. She is also on the Board of Directors for tech startups such as Averatek, Cambridge Touch Tech, Econic, Thingple, Global Power Tech and more.
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1) Climate: in 20 years, convert bio-based feedstocks into polymers that can displace 90% of today’s plastics and other commercial polymers
2) Supply chain: in 20 years, more than30% of US chemical demand should be via sustainable and cost-effective biomanufacturing
3) Cross-cutting advantages: in five years, sequence the genomes of one million microbial species and understand the functions of more than 80% of newly discovered genes
As reported by Forbes in Sep 2022: “The U.S. bioeconomy is booming. Valued at nearly one trillion dollars and predicted to grow globally to over $30 trillion over the next two decades, bioproducts now include everything from the food that we eat to the vaccines we put in our arms.”
Can these bio-material goals be achieved?
The biotech space is the next big race between China, the US, and Europe. The industry must be well prepared for disruptions in the next decade or two. The goals are ambitious and the challenges are clear:
For (1), replacing 90% of today’s plastics with bioplastics, industrial and process transformations lay ahead for chemical leaders such as BASF, SABIC, and Arkema.
For (2), with at least 30% of the chemical demand in the supply chain to come from bio-manufacturing, plans to develop bio-based resources must be in place, starting now.
For (3), to sequence one million microbial species in five years, having 80% of these functions understood means the entire bio-engineering process must be accelerated through technology.
With the bio-manufacturing transition and policy changes taking place, the industry must brace for impact. Many sectors aren’t ready. Take plastics manufacturing: oil as a feedstock for plastics is cheaper than bio-engineered polymers. Oil-based plastic packaging remains a first choice for many consumer brands.
Synbio (Synthetic Biology) accelerates with tech
The key to achieving lofty biotech goals is the field of Synthetic Biology (Synbio). Synbio uses genetic engineering to alter a cell’s DNA to make target molecules for manufacturing. It plays a role in healthcare, has shown promise in energy, and is gaining traction in the consumer goods space.
Synbio has been attracting an increasing amount of venture capital, especially in recent years. One of the reasons is the progress of computing power. Bioinformatics, with computer science, the power of AI, and machine learning, combined with chemistry, physics, molecular biology, agriculture, and engineering science, are working together to deliver bio-solutions faster than ever.
Computing power supports the Synbio development cycle, which is to Design, Build Test and Learn (DBTL). Unlike conventional chemistry, this deals with living organisms. In R&D, scientists must develop, test, and study the effect of altering genomes, microbes, and enzymes, to eventually engineer them synthetically.
In the West, synbio startups have been altering conventional products and processes, transforming the material world, and contributing to the bio-manufacturing industry, from food to cosmetics, to health and wellness – but none has been profitable.
With Synbio, supply may no longer be constrained by the availability of raw materials. Companies can engineer and manufacture an infinite quantity of things, cell by cell, from scratch. Half a gram of cattle muscle could create as much as 4.4 billion pounds of beef – more than Mexico consumes in a year.
While synbio might seem to be a magic wand to pursue a fully organic, sustainable, and low-carbon future, challenges remain in its “need for speed”.
Two methods of Synbio development: full-cell (live cells) or cell-free (synthetic cells)
(1) Full cell (in vivo/live cells)
Using live cells (full-cell) in a traditional process, scientists start with a design, then build the microbes, test them, and then record the results. The whole cycle repeats until the desired results are achieved. However, the fermentation process is complex, influenced by the control of culture and process parameters. Sometimes if the control isn’t managed well, batches may fail, affecting amplification.
Full cell processes keep cells alive in the entire development process, which limits the volume of chemicals produced on each course. There’s also a need to isolate the product from the rest of the cell (as cells have their processes to keep themselves alive) through protein purification, and is limited to products that aren’t toxic to cells. After fermentation, cells are broken down, and then purified to extract results.
It’s complex, and labor- and time-intensive.
(2) Cell-free (in vitro/synthetic cells)
The cell-free method is a new frontier, where the same process is conducted without a microbial environment (less time & complexity). Cell-free systems can be defined as platforms where biochemical reactions occur independently of living cells. Cell-free systems can be extract-based or enzyme-based.
The synthetic process replicates the basic functions of a living cell. In scientific terms, there’s no limit to the monomers to convert. Instead of a traditional 20% output, the cell-free process could allow researchers to achieve 90% output. Cell-free platforms are not restricted by limits for supporting life.
With cell-free formats, scientists can easily control and access protein synthesis with in-vitro bio systems without membranes, and achieve metabolic manipulation to enable inexpensive ATP generation or incorporate unnatural amino acids.
But there’s a catch: the cost is high.
Is there a better format?
The cell-free format is easier to manage, and results yield much quicker. The full-cell format is much slower, but the cost is lower as well – essential for startups tight on funds. To make the best of both, companies can combine the formats in their process: synthetic pathways designed, tested, and optimized in cell-free systems first, then transplanted to living cells for optimization, and then upscaled.
The Chinese synbio space
We’ve also looked at dozens of startups in the Chinese synbio industry. From the data, we zoned Chinese synbio startups across two areas: platform vs products, and those in the market for more than or less than five years.
No companies are doing just pure platforms. All Chinese synbio startups are running platforms and products, even if platforms remain their core expertise. The reason behind this? A matter of survival, since research and breakthroughs take time. Typically, it takes over five years to properly research and develop a discovery.
While there are Chinese synbio companies spanning the cell-free and full-cell formats, we haven’t encountered any startup in the cell-free space with a market product valued at more than USD 500 million.
There is great potential in the cell-free format to deliver a wider array of possibilities for the materials industry. Cost remains an obstacle. Full cell formats remain affordable for R&D, even if they’re cumbersome and time-consuming – part of the reason behind the delays in bio-material developments.
Synbio is in its own DBTL phase
So, it seems the Synbio industry itself is in the Design, Build, Test, Learn phase – cycling until it’s able to achieve breakneck efficiencies to deliver the breakthroughs needed for the bio-economy. But with constant advances in AI, computing technology, production techniques, and most importantly, embracing the cell-free format, achieving bold goals doesn’t have to be a far-fetched dream.
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