Gene synthesis Manual: building knowledge, promising

Gene Synthesis Handbook¬† – “building to know”: refers to the rational design, transformation or re synthesis of biological systems according to specific goals under the guidance of engineering ideas, that is, the engineering of biology, involving the intersection of biology, bioinformatics, chemistry, computer science and other disciplines. In short, it is to produce all kinds of desired products through the design at the DNA gene level through the multi omics method. The main technologies to be solved are: 1) mining/synthesis of key elements (DNA sequences); 2) Optimization of chassis cells (selection and transformation of strains); 3) Construction and product identification of metabolic pathway/gene expression pathway; 4) How to separate, purify and scale up production. And the whole process is closely related to algorithms such as machine learning and the completeness of biological databases.

The downstream application fields of synthetic biology are diverse

Based on the principles and technical methods of synthetic biology, there are three types of Companies: 1) developing enabling technologies, such as DNA synthesis and sequencing; 2) Manufacturing of DNA components and integrated systems, such as software services; 3) Use the synthetic biology platform to produce the required products (medical, agricultural, consumer goods, food and beverage, energy, industry and other fields).

The focus of different fields is different. The traditional chemical energy and food fields pay more attention to their cost reduction and efficiency enhancement capabilities, while the pharmaceutical field pays more attention to the product quality effects, such as protein targeting, pharmaceutical properties and other indicators.

Core technology of synthetic biology

Gene design is the underlying technology and also an essential technology for the development of synthetic biology: the vast majority of natural products with biological activity determine the biosynthesis of many gene elements are not clear, so it is particularly important to dig out the key gene elements in the synthetic pathway. According to the general chemical reaction principle and the known intermediate structure, supplemented by isotope tracing, the possible biosynthetic pathway can be inferred. Strain transformation: how to select the most suitable strain and how to transform the most suitable strain. Identification of product functional properties: there are many kinds of products, and the functional identification is unique and difficult. For strains whose genetic operation means are not mature and it is difficult to achieve (multiple) gene editing, cloning candidate genes and expressing them in heterologous systems, providing substrates by endogenous production or exogenous addition, and then analyzing and identifying the products by chromatography, mass spectrometry, nuclear magnetic resonance and other technologies, so as to determine the catalytic activity of enzymes is currently a common means. Separation and purification, scale-up and mass production: it is also difficult to expand production from the experimental stage. Future direction: to establish a learning feedback mechanism for the overall process by combining computer technology.

The core technology of synthetic biology is multidisciplinary, and most enterprises only have some abilities

Gene design – Key Enzymes of compound metabolism pathway + various types of proteins. The understanding of metabolic pathway/gene expression pathway is the basis. On August 10, 2022, Professor Sang Yup Lee, a well-known scholar of synthetic biology, published an updated list of chemicals that microorganisms can participate in synthesis. All available biological and chemical reaction pathways are compiled, including 532 compounds and 580 reactions, including 438 biological reactions and 142 chemical reactions respectively.

Development of synthetic biology

Phase I (before 2005): In the early stage of technology development, the representative achievement is the synthesis of artemisinin precursor in E. coli. The second stage (2005-2011): basic research has developed rapidly, and the annual patent application volume has not increased significantly compared with that before. The research and development of synthetic biology is generally in the stage of deepening the engineering concept, attaching importance to the enabling technology platform, and accumulating engineering methods and tools, reflecting the early development characteristics of “Engineering Biology”. The third stage (2011-2015): the efficiency of genome editing has been greatly improved, the downstream application fields have also begun to expand, and the importance of synthetic biology technology has been increasing. The fourth stage (after 2015): the concept of “design build test learn” in synthetic biology is proposed, the degree of multidisciplinary integration is deepened, the capital market is accelerated, and the industry enters an accelerated development period.