Team:SCU-China/Public/ACMA
HUMAN PRACTICE
ACMA
In 2019, we held the Sichuan University 2019 Architects Competition of Microorganism Application (ACMA): Microbes and Biosynthesis of Natural Products, which is a theoretical design competition. The ACMA uses iGEM's research thought for reference and encourages students to solve the problems of real-life by using kinds of subjects' knowledge.
After listening to the designs of other students in ACMA, we realized that we need to simplify our genetic circuits and reduce the metabolic load of microbes.
We had held the Sichuan University 2019 Architects Competition of Microorganism Application: 'Microbes and Biosynthesis of Natural Products' from June to September. This competition required contestants to participate in the competition in groups. And each group should design their project about the biosynthesis of natural products. Then the groups took part in the defense to present their project. Finally, based on their project feasibility, creativity, safety and so on, the groups were awarded different prizes.
For the first defense, there are 12 groups joined in it. And 6 teams were chosen to attend the final. The final was held at Jiang'an Campus of Sichuan University. About 10 professors attended as judges. After the final defense, one gold award, two silver awards and three bronze awards were issued.
We have also written a guide on ACMA for other teams' reference.
Abstracts of projects awarded gold, silver and bronze are listed as followed.
Gold
Smart insulin, a conjugated molecule of corosolic acid and quercetin synthesized by Saccharomyces cerevisiae.
Diabetes is one of the most normal chronic diseases in modern times. But if insulin is not used properly, dangers such as hypoglycemia can occur, which can lead to death in severe cases. Therefore, we hope to design smart insulin that can not only allow glucose to enter cells but also inhibit the glucose entry when glucose is normal and prevent hypoglycemia. Corosolic acid is derived from crape myrtle, and has a physiological function similar to insulin, which is called "plant insulin". Quercetin, found in flowers, leaves, and fruits of plants, has been shown to inhibit glucose transport. So, we chose corosolic acid as an insulin analogue; and Quercetin ACTS as a glucose transport inhibitor analogue.
We wanted our smart insulin to dynamically control blood sugar levels, so we wanted to couple these two small molecules. Based on their chemical and biological properties, we intend to join the two molecules in the form of covalent bonds.
Silver
Construction of a controllable nicotine-producing transgenic yeast.
In this project, the metabolic pathway of tobacco synthetic nicotine will be constructed in Saccharomyces cerevisiae, so that it can controllably synthesize the nicotine, a natural insecticidal substance. Firstly, we use genetic engineering to transform Saccharomyces cerevisiae to make it able to synthesize nicotine. Then riboswitch is designed to sense indole, which is a kind of volatile organic compounds released when plants are suffering insect-inflicted injury, to control the expression of metabolism-related genes in Saccharomyces cerevisiae. This can make the genetically engineered yeast able to sense pests and synthesize nicotine, and automatically die when there are no pests, which can make up for shortcomings of chemical pesticides such as the environmental pollution, killing beneficial insects, destroying the ecology, toxic substance residues and so on.
Biosynthesis of sea cucumber saponins.
Sea cucumber saponins are a kind of secondary metabolites existing in sea cucumbers. For human beings, they can improve immunity, inhibit pathogens and kill tumor cells, so they have important medicinal value.
However, because of the scarcity of sea cucumber saponins in sea cucumbers and the high price of sea cucumbers, sea cucumber saponins can’t be widely popularized as drugs, so this project uses Saccharomyces cerevisiae according to the known metabolic pathway of sea cucumber saponins. The genes of key enzymes were introduced into yeast cells by means of genetic engineering. 2, 3-epoxy squalene, a precursor of sea cucumber saponins in yeast, was metabolized to produce sea cucumber saponins, and the engineering bacteria which could produce sea cucumber saponins were constructed, in order to achieve the goal of mass production of sea cucumber saponins.
Bronze
The co-fermentation of wogonin and breviscapine.
Wogonin and breviscapine are flavonoids extracts of traditional Chinese medicine, which have high clinical application value, but the current supply can’t meet the increasing demand. Studies have shown a gene pathway that can be used jointly in the catalytic process from L-phenylalanine and L-tyrosine to wogonin and breviscapine precursors. In addition, some scholars have analyzed the key genes such as F7GAT, UDPGDH, and OMT5, which are involved in the final pathway of breviscapine and wogonin synthesis. We hope to use microorganisms to design a metabolic pathway and synthesize breviscapine and hanxanthin simultaneously by means of common genetic pathways and synthetic biology. Considering that the intermediate metabolites naringin and naringin can also be used for the synthesis of other flavonoids derivatives, Escherichia coli from the substrates to naringin and naringin and Saccharomyces cerevisiae for the synthesis of hanafensin and breigeron respectively, so as to facilitate the synthesis of other flavonoids derivatives in the future. Finally, wogonin and breviscapine will be synthesized by co-culture.
High efficiency ethylene production project based on quorum sensing.
In order to solve the sustainability problem of ethylene production caused by the shortage of oil supply in China and the shortage of oil resources in the world, Escherichia coli was selected as engineering bacteria and microorganisms were common by genetic engineering. Ethylene synthesis pathway-EFE gene (an ethylene forming enzyme gene) in the EFE pathway is introduced into Escherichia coli for expression, and a-ketoglutaric acid is added to increase the yield. In this paper, an engineering strain of Escherichia coli which can synthesize ethylene efficiently was designed.
Biofilm fermentation pigment production system based on pH transcriptional regulatory elements.
This project aims to use biosynthesis, microbial fermentation and related technologies to explore green, high yield, high efficiency, low cost, easy to operate and manage natural pigment food additive synthesis solution. The scheme ensures the safety and reliability of the synthesis process, maximizes the use of biological products in the production process and avoids the use of chemical raw materials, so as to reduce the potential harm to human health and improve the market acceptance of the products.
