Synthetic biology is an interdisciplinary field, and it is also a package of technologies and methods, combining the knowledge of multiple disciplines such as biology, engineering and computer science, and more and more companies, research institutions and entrepreneurs are investing in the research and development and application of synthetic biology.
Looking back on 2023, synthetic biology will develop in depth, gradually enrich product categories, and rapidly deploy various vertical fields. On the occasion of the new year at the end of the year, when various companies have developed in-depth technology, when many companies are confused by "product selection", we begin to determine whether synthetic biology has a "winner-takes-all" path similar to the development process of the chemical industry. In this process, we found that platform capacity building is crucial in the implementation of synthetic biology in China.
MIT Technology Review China Tidetron Biotech jointly released the "2023 Synthetic Biology Full-Link Platform Capacity Building Research Report".Focus on the capacity building of the full-link platform of synthetic biology, focusing on the driving force and core competence of platform development, as well as the characteristic industrial transformation of platform development in China.
We hope to see synthetic biology companies use engineering R&D capabilities to develop multi-pipeline products, effectively connect the scale-up production of factories, stabilize production capacity for the market, and use an open and diversified cooperation model to realize the integration of research, production and marketing, and the layout of the whole industry chain, forming a complete "big platform" that connects upstream and downstream. From a single product or application field to multiple products and a wide range of application fields, with a benign industrial ecology and comprehensive capabilities to achieve sustainable development of synthetic biology.
Synthetic biology has moved from a single category to a full-link industrial ecology
The long progress of life sciences has given birth to synthetic biology, which integrates biological theory and engineering applications, and provides a historic opportunity for the human production and manufacturing paradigm: In the face of the severe environmental situation, human beings urgently need to change the development model of the existing industrial civilization, transform the traditional industrial production mode, and reduce the dependence on fossil fuels;Biomanufacturing based on synthetic biology is an important way to achieve carbon neutrality, and it is also a major opportunity for China to break through the bottleneck of petrochemical raw materialsBiomanufacturing based on synthetic biology has great potential for material and molecular innovation, expands the boundaries of human manufacturing capabilities, and leverages huge economic value.
From the perspective of investment and financing in the field of global synthetic biology, financing activities are still in the early stage, and companies are in the period of technology exploration and industrial experience accumulation, and the number of raw materials produced by synthetic biology is still small, and it has not yet been applied to end products on a large scale, and the returns it brings still have a certain cycle. In the short term, synthetic biology practitioners still need to work together to expand the market, and the transformation from technology to product and from product to sales is the pain point faced by enterprises focusing on the field of synthetic biology.
Table丨2022-2023 Financing of some synthetic biology companies in China.
Throughout the history of the chemical industry, many chemical giants have achieved great success through the path of platform development, and the construction of platform capabilities has enabled these companies to transform from traditional single product manufacturers to comprehensive enterprises with diversified product portfolios and wide application fields.
The same logic applies to the bioeconomy, where synthetic biology is still in the exploratory stage and there are still unknown possibilities for its development model. With the whole chain layout of technology landing, factory construction and production, product listing, industrial integration, etc., the boundary between traditional technology platform enterprises and product-oriented enterprises will tend to be blurred, and the overall trend is developing in the direction of "big platform". With the maturity of the technology platform, it is further necessary to open up the layout of the entire upstream and downstream industry chain, gradually form a full-link platform capability, and uphold an inclusive and open attitude, its benign industrial ecology and comprehensive capabilities are more conducive to sustainable development.
Figure丨Synthetic biology full-link platform capability (**deeptech).
The core capability of the construction of the full-link platform for synthetic biology
Core competencies of the technology platform
Diverse chassis cells:The modification of chassis cells is to serve the production of target products, and at the same time, in order to adapt to industrial-grade preparation, it is also necessary to consider the separation and purification of the production end. For example, based on the oligopeptide expression and purification method of E. coli display and endopeptide cleavage, an oligopeptide for display on the surface of the host bacteria was constructed, and the oligopeptide was linked to the display protein by endopeptide to induce the expression of the "display protein, endopeptide, oligopeptide" fusion protein, and after the culture and collection of E. coli, the internal peptide was cleaved to release the oligopeptide, and the oligopeptide was crystallized or dried after ultrafiltration. This process does not require cell fragmentation or protein purification, and E. coli can be reused, making it an efficient and simple oligopeptide production and purification process that is ideal for industrial-scale oligopeptide preparation.
Modular cell construction:Modular cell construction starts from the most basic biological components, and takes the biological components with specific functions as a "part module", and uses the building blocks to design these "parts modules" to form a new biological device, and the biological devices with different functions are connected in series, feedback, feedforward and other forms, and work together to form a more complex biological system, so as to perform specific design functions and realize the production of target products.
High-throughput automation tools:The high-throughput automation platform has evolved from the initial single equipment stage to laboratory automation and intelligence, but the automation of a single link does not have the ability to improve the overall efficiency, and it is necessary to integrate the equipment into the R&D platform system, and develop the pipeline according to the actual situation, accumulate technical experience and efficiency upgrades. In the service of multiple pipelines and different scenarios, through the accumulation of data and experience, the effect of "secondary development" is achieved.
Artificial Intelligence (AI) Empowerment:The application of artificial intelligence in the field of synthetic biology is becoming more extensive and deeper, from the initial "Xi" stage of synthetic biology, gradually expanding to the entire dbtl cycle, and is involved in engineering amplification and other fields. For example, the exploration of AI+ Life Science, combined with artificial intelligence, big data, and bioinformation technology, has designed the ITIDETRON AI engine at the cutting edge, and built six modules: active substance and strain identification, controllable gene expression, metabolic pathway design, controllable biosensing, enzyme design and transformation, and dry and wet experiments, to jointly overcome R&D problems and drive the rapid mass production of substances.
Large-scale production core capabilities
Efficient fermentation optimization scale-up:In industrial production, microorganisms need to be exposed to more complex and severe industrial environmental conditions to complete high-yield and high-efficiency production tasks, including substrate stress, metabolite stress, environmental pressure, etc. Artificial domestication, mutagenesis screening, directed evolution and other methods are still necessary means, and the path of "small-scale-pilot-mass production" is opened up through efficient optimization and amplification.
Large-scale fermentation technology:Using intelligent precision equipment clusters, bioreactor development, digital processes, and synthetic biology data-driven logic, traditional fermentation is promoted from extensive curve changes to more in-depth metabolic flow analysis.
Figure丨Synthetic biology full-link platform capability (**deeptech).
Multi-variety industrialization capabilities
In the highly competitive market, the ability to achieve rapid commercialization constitutes one of the core competitiveness and commercial barriers of synthetic biology platform capabilities. The commercial transformation process of the synthetic biology platform includes the whole cycle chain from basic research to final commercial consumption, which can be roughly divided into two levels: technology and business.
Figure丨Technology and business jointly empower the industrialization capabilities of multiple varieties (**public information, deeptech).
Through platform capacity building, synthetic biology companies can provide diversified products and achieve cross-industry coverage to meet different market needs, so as to expand market opportunities, improve enterprise competitiveness, avoid the risk of a single variety of industry cycles, and realize business diversification and revenue diversification. To achieve cross-industry coverage of diversified products, it is necessary to have advanced technical advantages, interdisciplinary team composition, keen market insight, perfect first-chain management and large-scale production capacity.
Diversified cooperation ability
In the global competitive environment, synthetic biology companies need to rely on the capacity building of the full-link platform and build a global industrial ecosystem through diversified cooperation to cope with the increasingly fierce challenges. By creating an open cooperation model with partners such as university research institutions, industry peers, and downstream product application companies, we can achieve resource sharing and cost optimization, accelerate product development and market promotion, expand business opportunities, accelerate the pace of innovation and development, and promote the progress and development of the industry.
Figure丨From 0-1 full-link solution model (**Tidetron Biotech).
Industrialization of the full-link platform for synthetic biology
The capacity building of the full-link platform connects the various development types of the synthetic biology industry, and we classify synthetic biology companies according to different product categories and pipeline numbers.
Enabling Technologies:The infrastructure in the field of biomanufacturing provides the basic support for biodesign and research. R&D, design and manufacturing enterprises of instruments and equipment, such as Beckman and other life science instrument companies;Synthesis, sequencing, database and other service companies, such as GenScript, Qingke Biotech, etc.
Technical service type:Focus on breaking through the circular iteration of DBTL to build an integrated platform for organism design and software development, and obtain microbial cell factories that meet the required traits. This model emphasizes technological innovation and platform construction, and provides R&D and technical support for synthetic biology, such as ginkgo, codexis, etc.
Large single item type:Occupy the market through core large products, focus on each link of the entire production chain, and focus more on the research and development, production and commercialization of one or several types of product categories. Such as Perfect Day, Cathay Biotech, etc.
Multi-industry chain application:It focuses on the layout of the whole industrial chain, multi-field application, integration of research, production and marketing, open cooperation, etc. In terms of technology, we will build a synthetic biology capability platform to enable enterprises to achieve rapid iteration and innovation of technology, and attract more innovators and ideas through an open and cooperative model, so as to form a wider product line and expand market space. At present, most of the innovative synthetic biology companies have established technology platforms and laid out multiple pipelines, but only a few companies focus on the integration of research, production and marketing and open cooperation, such as Tidetron Biotechnology.
Figure丨Synthetic Biology Industry Atlas (**Public Information, Deeptech).
Product selection and commercialization are driven by market demand
In the process of industrialization, "product selection" is considered to be one of the important challenges faced, from the selection to the success of research and development, often need to go through a long period of time, need to take into account the scale of production, access threshold, development difficulty, market demand and other factors, if the early product selection is not mature industrialization of the product, it means to bear the risk of research and development, manufacturing, sales, channels and products at the same time. Compared with overseas synthetic biology companies, which prefer to take technological innovation as the starting point of commercialization strategies, Chinese synthetic biology companies are more driven by market demand, and tend to choose the direction where the technology has been run, the degree of transformation is high, and the threshold is slightly lower to give priority to commercial transformation. The logic of these two starting points is correct, but having technology does not mean that technology can be turned into a market, and in many cases, the market ceiling of raw materials also determines the ceiling of the enterprise. If product selection and commercialization can be considered more comprehensively, there will be a broader space for development.
For the "stock substitution" and "incremental expansion", it is advisable to adopt different commercialization strategies
The market situation of synthetic biology in different application fields can be roughly divided into two categories, one is stock substitution, and the other is the incremental expansion of innovation, and the two types of markets have different requirements for products
Stock substitution:Due to the difference in the production process between bio-based products and traditional petroleum-based products, it involves bio-based impurity trace detection and purification of bio-based impurities, so that bio-based chemicals can effectively enter the existing chemical system.
Incremental Expansion:Taking high value-added products as an example, it is necessary to improve and compound on the basis of upstream raw materials to solve a series of problems and pain points that may arise in the application process of the active ingredient in the end product, and ensure that the active ingredient performs well in the end product.
Carry out applied research to open up a "one-stop" solution for synthetic biology
Regardless of stock substitution or incremental market expansion, it is necessary to carry out applied research on synthetic biological products, including basic research, formulation research and application, compliance and quality control, etc., and control every step from product development, product application to product launch with "high standards and systematization". At the same time, it is necessary to establish a comprehensive and systematic testing technology system to support the "tempering" of products before they are launched, and strictly control product quality from the R&D end.
Figure丨Basic process of formula research and application (**Tidetron Biotechnology).
Tidetron Biotech - a platform-based development enterprise for multi-industry chain applications
By building a synthetic biology platform, based on technology, taking production as the starting point, taking products as a breakthrough, and taking the market as the guide, the four major sectors promote each other and accelerate positively, taking the lead in realizing the integration of research, production and marketing, the layout of the whole industry chain, and sustainable development. Focusing on the field of "medical and food beauty and safety", we will build a global synthetic biology industry ecology with partners, and at the same time, the open cooperation of the platform strengthens industrial integration, and feeds back from the market industry to the R&D end of technological innovation.
Figure丨Tidetron Synthetic Biology Platform (**Tidetron Biology).
【Technology】Based on technology, break through the bottleneck of mass production in the industry
Tidetron has built an automated R&D platform, which contains strain libraries, component libraries, AI engines, etc., which greatly improves R&D efficiency and links every step of R&D and production. The formation of upstream components, strain banks and other platforms to help the construction of cell engineering; The mid-end focuses on the efficient cyclic operation of the synthesis pathway, metabolic route, and expression carrier of the target product, and improves the fermentation efficiency through microfluidic and other platforms. The downstream has built a perfect small-scale test-pilot-mass production path. Achieve mass production capabilities for a variety of cross-domain products.
Strain Libraries & Component Libraries:Through the self-built strain library and component library, based on the gene big data platform, the chassis cells can be assembled and modified according to needs, providing basic resources and data reserves for the rapid construction of a "cell factory" for synthesizing target substances.
AI ** Model:Combined with high-throughput sequencing and artificial intelligence, the independent research and development of active peptides and mining models have the characteristics of high accuracy, good stability and wide practicability in active substances, which can identify the functions and uses of strains in nature and provide strong support for the construction of "cell factories". In November 2023, it was the first to open up AI antimicrobial peptides** and mining systems. Antimicrobial peptide (AMPS) is a small molecule active peptide with broad-spectrum antibacterial effect, which is not only resistant to acid and alkali, antitumor, and antiviral, but also not easy to develop drug resistance. However, due to its short sequence, high diversity and low similarity, the research of antimicrobial peptides still needs to rely on repeated experimental verification to a large extent, which gives AI the opportunity to empower it.
Bioengineering Techniques:A variety of gene editing tools such as CRISPR-CAS are used to improve the synthesis efficiency of the "cell factory" in an all-round way, combined with genetic engineering, enzyme engineering and other technical means to realize the construction and optimization of metabolic pathways in chassis cells, and finally form a sample bank of as many engineered bacteria as possible, which greatly improves the success rate of obtaining target strains.
Directed Evolution and Microfluidics High-throughput screening:Through the combination of microfluidics and directed evolution, the traditional "rational design" was broken through, and the directed mutagenesis process was introduced into the "cell factory" synthesis pathway. The current microfluidic platform can achieve a throughput of 10 to 9 cell days, which is 3-4 orders of magnitude higher than traditional screening methods, and the screening process has also been shortened from years to months.
【Productivity】Large-scale mass production to achieve stable production capacity**
Through the construction of its own intelligent factory, the R&D substances are improved through a series of processes, and the optimal strains are rapidly fermented and mass-produced in a customized intelligent fermentation system, and the products are separated and purified to obtain target substances with high purity, good activity and stable quality. At present, it has covered the production lines of beauty, food, bulk raw materials, industrial preparations, etc., with an annual production capacity of more than 10,000 tons.
Figure丨Production process - taking erythritol as an example (**Tidetron Biotechnology).
【Product Strength】Multi-pipeline to reach the "medical, food, American" and multi-field
Relying on the universality of the underlying technology and the back-end scale-up production experience, more than 50 kinds of raw material products have been realized in the warehouse, meeting the needs of "medical, food, beauty and safety". In terms of product selection logic, maintain market acumen and grasp the actual demand, and gradually expand from consumer goods and high-value products to bulk raw materials. Build a research and application center to empower products in an all-round way, conduct basic research, formula research and application, and compliance quality control, and provide customers and partners with high-quality green raw materials and full-link solutions.
Figure丨Demand-oriented, green applications cover medical and food Mei'an (**Tidetron Biotechnology).
【Market Power】Jointly build a global synthetic biology industry ecology
From product to market:Tidetron has a stable first-class system and a strong sales and new business development team, has opened up 100+ factories and brands around the world, and is entering the leading brand first-class system, with domestic partners such as Evespring, Yilihui, Wanglaoji, Yetai, Chunguang, etc. The cooperation model is mainly based on services such as raw materials, formula development and product full-link solutions.
From technology to market:Together with 10+ academicians and 30+ experts, Tidetron has cooperated with Sun Yat-sen University, Jiangnan University, Nanjing University of Technology, Bio Island Laboratory and other universities and scientific research institutions to carry out synthetic biotechnology transformation. For example, with Academician Chen Jian of Jiangnan University, the Joint Research Center for Synthetic Biotechnology has been established to make R&D breakthroughs and transformation of substances such as breast milk oligosaccharides, in addition to Sun Yat-sen University-Tidetron Bioengineering Biotechnology Joint Research Center, Future Biomaterials Joint Research Center, and Guangdong-Hong Kong-Macao Greater Bay Area Synthetic Biology Innovation Technology Transformation Center.
In the study of the capacity building of synthetic biology platforms, we can see an initial trend:With the maturity of the technology platform, synthetic biology platform enterprises gradually have the ability to develop multi-pipeline products, and connect the enlarged production of their own factories, stabilize production capacity externally, and open up diversified cooperation models to realize the integration of research, production and marketing, and the layout of the whole industry chain, and form a complete "big platform" by opening up the upstream and downstream. Its benign industrial ecology and comprehensive capabilities are more conducive to sustainable development.
The core objectives of the capacity building of the synthetic biology full-link platform:Improve the application efficiency of synthetic biology, expand the application scope and accelerate the industrialization process. By building comprehensive industry core capabilities, synthetic biology can better meet the needs of multi-product, multi-industry and multi-field industries, and promote innovation and sustainable development.
Required synthetic biology platform capabilities include:Complete and efficient technology R&D platform, whole industry chain layout, integration of research, production and marketing, covering R&D capabilities, large-scale mass production capabilities, product application capabilities, commercialization capabilities, etc.
In the development process of synthetic biology for more than 20 years, synthetic biology is not only a package of technologies and methods, but also a discipline at the intersection of science and technology and industry. It is necessary to increase R&D investment on technology platforms to actively promote technology development; At the same time, it is necessary to actively expand open and inclusive cooperation, create a soil for communication, and enable research results to be efficiently transformed into products and services with commercial value and landing. From a single product or application field to multiple products and a wide range of application fields, with a benign industrial ecology and comprehensive capabilities to achieve the sustainable development of synthetic biology.
About Tidetron
Tidetron Biotech is one of the world's first platform-based synthetic biology companies to achieve mass production of a variety of substances. By building a synthetic biology platform, based on technology, taking production as the starting point, taking products as a breakthrough, and taking the market as the guidance, the four major sectors promote each other and accelerate positively, and take the lead in the industry to realize the integration of research, production and marketing, the layout of the whole industry chain, and sustainable development. With efficient, safe and environmentally friendly biomanufacturing methods, we focus on meeting the new needs of the people for "medical and food beauty and safety", and work with partners in various fields to build a global synthetic biology industry ecology.