Nature : Six biosynthetic products that are changing the world

Nature : Six biosynthetic products that are changing the world.

Today’s newer technologies are gradually transforming previously conceptualized ideas into products that can make people’s lives more convenient.

Synthetic biology, as a representative among them, has also quietly changed our usual crops, foods, resources used and synthetic drugs.

Today’s newer technologies are gradually transforming previously conceptualized ideas into products that can make people’s lives more convenient.

Synthetic biology, as a representative among them, has also quietly changed our usual crops, foods, resources used and synthetic drugs.

Scientists predict that by 2030, all of our daily food, clothing, housing and transportation will most likely come from our own biosynthetic products.

Recently, Professor Christopher Voigt from Massachusetts Institute of Technology published an article titled: Synthetic biology 2020–2030: six commercially-available products that are changing our world in Nature communications. The article lists six in the period 2000-2020.

The most typical and most representative of the comprehensive development of artificial biosynthesis is the product that has come out, has been facing the market.

Among them, the first three products are substances produced through engineered cells or enzymes, and the latter three are engineered cells. Their respective technologies are also in 2018 (directed evolution technology) and 2020 (gene editing). Won the Nobel Prize. The author hopes to show how much technology has brought to people’s lives by covering the surface.

Bleeding Burger

Impossible Foods recognizes that blood, especially iron-containing blood matrix, is very important to the taste and taste experience of burgers. They found that some plants sometimes “bleed” when their roots are cut.

Therefore, the company thought of biologically transforming Pichia pastoris to produce soybean hemoglobin, which can be used as an ingredient of artificial meat food to improve the taste and aroma of meat.

The improvement of the product chain requires a variety of technologies, including DNA synthesis, Gibson assembly, genetic engineering and so on.

In comparison, the plant burgers made by the company only require 4% of the land used to make beef patties, and only 11% of its greenhouse gases are emitted.

Currently, their products have been put on shelves in more than 30,000 restaurants and 15,000 supermarkets all over the world.

In terms of macro-methodology, advances in metabolic engineering can diversify natural metabolic pathways into production hosts.

And by modifying yeast to make it compatible with the production host, or making it a new host to help production, it is also giving birth to more new generations of products, such as vitamin E and stevia (Replace traditional sugar) ,whey (Milk whey, people who are sensitive to lactose can also eat it).

Genovi – blood glucose inhibitor

Genovi is a blood sugar control agent suitable for patients with type 2 diabetes. It mainly promotes insulin secretion by inhibiting the DPP-4 enzyme.

It ranks 95th among the most prescribed drugs in the world, with an average annual rate of approximately 1 million prescriptions and 1.35 billion US dollars in sales.

The drug molecules have stereo-oriented amine groups, which require heavy metals and high pressure reactions in the manufacturing process.

Therefore, from a chemical point of view, it is difficult to produce in large quantities.

However, scientists discovered that by using the R-selective transaminase on Arthrobacter bacteria and using computer simulation to realize the combination with new substances to promote directed evolution, the activity of the enzyme can be optimized, and the final transaminase can achieve 27 amino acid mutations, perfectly reaching 99.95. % Product purity (Excessive optical isomers).

This type of method is now also used to produce the HIV antiviral drug-Islatravir, which is currently undergoing phase 2 clinical trials.

Hyaline–new biofilm

Zymergen has developed a polyimide film, which is a new type of biofilm that can be applied to electronic products. Polyimide is generally known for its thermochemical stability and good mechanical properties and other material properties.

However, the material itself has the problem that the material cannot be made transparent due to color defects, which also restricts its use in the material field. The main reason for development.

However, the company has developed a transparent polyimide film. The film is not only elastic and good in mechanical properties, but its product solution also has very good mass production, which is very suitable for the new generation of electronic equipment (For example: foldable smart phones, wearable devices, etc.) On promotion.

At present, this product has been used in some flexible circuits, display touch sensors and printed electronic products. This type of film is made of diamine monomers synthesized by an excellent enzyme strain after bioengineering.

The company is building an automated machine system that can produce millions of enzyme strains at the same time. And through the guidance of artificial intelligence, they can also learn from the experience of failed products to further optimize the design of the next round of enzyme strains.

Such cutting-edge technologies are constantly emerging all over the world, accelerating the pace of biosynthetic project development.

PROVEN–Nitrogen Fertilizer

Every farmer understands that the necessary condition for high crop yields is to add nitrogen to fertilizers/crops. The traditional method of producing nitrogen once occupied 1-2% of the world’s energy.

Although there are bacteria that can fix the nitrogen in the air as a biological nitrogen fertilizer, they cannot be used in cereal crops. (For example: corn, wheat, rice) Used on.

Pivot Bio first developed the first generation of biological fertilizers for corn (Based on γ-KV137 Proteus acting on the roots of corn to provide the necessary nitrogen fixation genes). However, when crops really need nitrogen, such genes still cannot provide it.

Therefore, the company used biosynthesis to genetically edit γ-KV137 Proteus, reshaping its genome, making it an active ingredient in liquid fertilizer, and finally achieving the goal of nitrogen fixation. The advantage of PROVEN products is to reduce the demand for chemical fertilizers (12 kg/acre) , And also increased production to 5.8 bushels (About 157.9 kg). 

What’s more eye-catching is that, unlike traditional chemical fertilizers, the effect of rainwater does not pollute the fertilizer’s nitrogen into the groundwater, nor does it become the greenhouse gas N2O and emit it into the atmosphere. In 2020, the use area of ​​PROVEN has reached 250,000 acres, and plans to expand to millions of acres in 2021.

Kymriah–a new treatment for leukemia

In medical treatment, engineered cells are regarded as the “third pillar” of the medical profession. Kymriah is the first such therapy to be approved by the FDA, and it is also known as CAR-T therapy.

The therapy mainly consists of extracting T cells from patients and using genetic engineering technology to transform T cells so that they can express tumor chimeric antigen receptors (CAR), And then return to the patient’s body. CAR-T cells can specifically recognize tumor cells in the body, and then release a large number of various effectors through immunity to kill tumor cells. These modified cells can usually last for decades in patients.

Kymriah therapy expresses the CD19 antigen on fusion cancer cells, and transforms the patient’s T cells through lentiviral vectors. The remission rate for patients who relapse or is incurable is as high as 83%. This type of therapy and similar Yescarta (Developed by Gilead). Therapies will generate approximately $1 billion in sales in 2020.

In the summer of 2020, there are already 671 CAR-T therapies in clinical trials, most of which are for blood cancer, and more and more therapies are being used to treat solid tumors, viral infections and other diseases. .

Calyno-high oil soybean oil

Calyno oil is the first vegetable oil product extracted from plants that have used gene editing technology and can enter the US food supply chain. Soybean oil itself occupies 90% of seed oil, but its linoleic acid content is particularly high. The linoleic acid substance itself is unstable and will be rapidly degraded at the frying temperature.

On the other hand, although it can be partially hydrogenated, it still produces unhealthy trans fats.

Calyxt re-edited soybean genes to make two fatty acid genes inactive, thereby reducing the production of corresponding linoleic acid. Genetically edited soybeans produce 80% soybean oil containing oleic acid, while unedited soybeans can only produce 20%.

Moreover, the gene editing technology used by the company greatly simplifies regulatory review due to relatively few gene deletions and no DNA recombination. Today, Calyno gene-edited soybeans have been planted on about 100,000 acres of land.

Imagine the future

Perhaps in the future world, we are unlikely to be flying in a bee helicopter, living in towering trees, or flying a squid-shaped spaceship between stars.

The author can really feel that what is most likely to appear in the future is: new insect materials used in the aerospace field, the toxic glue in the field of building materials is replaced by mycelium, and NASA can use synthetic biology in space travel.

Food and medicine are produced in space. And, as the population continues to increase, fermented foods will continue to increase accordingly. In the manufacture of consumer goods, sugar may no longer be a stable raw material.

In the next decade, the new generation of microbial chassis may be expanded in demand, so as to be able to use alternative energy (Plastic waste, carbon dioxide in the air). In exchange for carbon raw materials.

Fresh water may also become a very limited resource in the field of fermentation, but perhaps we can also develop the halophilic bottom of a bioreactor grown in seawater for fermentation.

Of course, cell-free manufacturing can also reduce water use and physical footprint, as well as reduce the instability of the cell system.

From a practical level, the six materials described above have been able to bring in annual sales of 2 billion US dollars. The author can predict that by 2030, writing this type of review may require reviewing hundreds of products. What about after 2030?

The author believes that the establishment of complex systems will become a mainstream, not a single cell or a single system. Whether in the agricultural industry, food industry, construction industry, or artificial intelligence industry, different fields need to be involved and cooperate with each other to solve various problems.

It is true that these assumptions are very beautiful, but to realize them, we need more complete design concepts and design tools, combined with simulation and real environments, to be able to truly turn ideals into reality.

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