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Reconstruction of the Bacterial Metabolic Pathway by Using De Novo Genome Assembly Technology

An innovative technology that can be used to solve the problems related to the depletion of energy and oil

"Based on the calculation of the currently-known reserves, the amount of oil will be depleted after 54 years while that of natural gas and that of coal will be depleted after 63 years and 112 years, respectively. Around the world, many nations have been focusing on the development of alternative or renewable energy sources. However, the creation of CO2 from the consumption of fossil fuel energy could lead to the emergence of various problems related to global warming. A more important point is that theMore importantly, the depletion of fossil fuels will make it impossible to produce products such as plastic, paint, and clothes. Furthermore, the production of medicines for the treatment of diseases will be threatened. Creating a method to transform CO2 into value-added chemicals through the use of solar energy (or solar- energy- derived electricity) and bacteria is an extremely challenging task. If it becomes successful, it will be possible to solve all the problems related to the depletion of energy and oil.”

Development of sustainable chemical production technology

Since there is a lack of renewable alternative energy technologies and since various problems appear due to the depletion of traditional fuels, there is now an urgent need to develop alternatives to fossil fuels. As a result, such technologies as those for the reduction of CO2 are in high demand. This is because, even if though other energy sources such as the solar energy, hydroelectric energy, and tidal energy are being considered, they fail to fully replace fossil fuels, which can be used to produce various petrochemical products. Although various fields of research, including CCS (Carbon Capture & Storage) technology for the reduction of greenhouse gases, have been actively carried out for the isolation of CO2, it is still hard to find a more fundamental solution for the reduction of CO2.

Therefore, the KIB research team led by Professor Byung-Kwan Cho has developed a method to reconstruct the bacterial metabolic pathway, which utilizes CO2 to produce other chemicals, in order to reduce CO2 emissions and to provide an alternative means of producing chemicals that were traditionally extracted from fossil fuels.

The technology is related to the process of transforming CO2 into various chemicals by applying solar energy source (as a form of electricity) to bacterium. Since CO2 is a stable chemical substance, it is necessary to apply an outside energy source to convert CO2 into another substance. The results from Professor Cho’s team are important since they focus on the high-throughput analysis of the bacterial genomes, which can be used for the utilization of CO2 and provide a support for the development of intelligent bacterial systems with a higher level of efficiency, establishing a base for the technologies related to the sustainable production of chemical products. With such an effort, the research team has received global attention for its research results. For the past three years, the team has researched the transformation of CO2 into a value-added chemicals by using bacteria and solar energy as the energy source with support from KAIST(KIB) and the Intelligent Synthetic Biology Center, ar (the global frontier project carried out by the Ministry of Science, ICT and Future Planning).

The R&D process can be distinguished into three stages. The first stage is related to the excavation and cultivation of bacteria, while the second one is related to the high-throughput genome sequencing, and the third one is related to the construction of the metabolic network through the sequence data analysis. Since the homoacetogenic bacteria metabolize CO2 in the air and synthesize hydrocarbon for the organism, they could can grow in environments with no organic nutrients. However, since they cannot live in environments with oxygen, it took more than two years to develop the incubation facilities and master the necessary techniques for the successful cultivation of these bacteria in the laboratory. The R&D process can be additionally described as follows. The genome separated from the cultivated bacterial cells is fragmented into small pieces, which that is are then rapidly sequenced using a next-generation sequencer. At that time, computational analysis is carried out in order to find all the overlapping parts of thousands or tens of thousands of short DNA sequences with the purpose of figuring out their overall genomic order. (In such a case, each piece, a so so-called “read”, shows the a length of 50 to 200 base pairs of DNA.) The assembly of short DNA sequences produces about one hundred of100 contigs. (Each contig is a set of overlapping DNA segments that together represent a consensus region of DNA.) The genome length of each bacterium is about 1,000,000 to 10,000,000 base pairs. As a result, it takes a few hours for some cases and a few weeks for others to connect the pieces with the length of 50 to 200 base pairs to generate the contigs. Therefore, it is necessary to be proficient not only in experiments related to life science but also in computational calculations. Also, since the genomic order of the short DNA sequences is different for each bacterium, the equations required for the solutions of the computational calculations slightly differ.

The research team led by Professor Byung-Kwan Cho found, through a complicated process, the an equation that is appropriate for bacteria and carried out similar calculations in order to find genes from the contigs. As a result, by using every piece of information contained in the previous genetic database, the research team figured out the genome sequences of new bacteria and found thousands of genes at once. Among the thousands of genes found through this process, the Wood-Ljungdahl pathway, in which homoacetogenic bacteria metabolize CO2 as organic matter, was found and re-organized by using bioinformatics.

By using the technology for reconstruction of the bacterial metabolic pathway from de novo genome assembly, it is possible to obtain information regarding the genes existing in the subject micro-organisms without assembling the analyzed one complete genome. As a result, it is possible to interpret a large capacity of genomes at high speed. Also, we can establish a database for the metabolic pathway of homoacetogenic bacteria for the CO2 fixation, whose genome information is largely unknown. This information could be used as a platform for any future research regarding the production of useful materials. Furthermore, it could become the foundation for any future technology focusing on solving environmental problems and problems related to the depletion of energy and oil.

Prof. Cho, Byung-Kwan
2013 Annual Report

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