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Unveiling the Distinctive Features of Industrial Microorganism
KAIST researchers have sequenced the whole genome of Clostridium tyrobutyricum, which has a higher tolerance to toxic chemicals, such as 1-butanol, compared to other clostridial bacterial strains. Clostridium tyrobutyricum, a Gram-positive, anaerobic spore-forming bacterium, is considered a promising industrial host strain for the production of various chemicals including butyric acid which has many applications in different industries such as a precursor to biofuels. Despite such potential, C. tyrobutyricum has received little attention, mainly due to a limited understanding of its genotypic and metabolic characteristics at the genome level. A Korean research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) deciphered the genome sequence of C. tyrobutyricum and its proteome profiles during the course of batch fermentation. As a result, the research team learned that the bacterium is not only capable of producing a large amount of butyric acid but also can tolerate toxic compounds such as 1-butanol. The research results were published in mBio on June 14, 2016. The team adopted a genoproteomic approach, combining genomics and proteomics, to investigate the metabolic features of C. tyrobutyricum. Unlike Clostridium acetobutylicum, the most widely used organism for 1-butanol production, C. tyrobutyricum has a novel butyrate-producing pathway and various mechanisms for energy conservation under anaerobic conditions. The expression of various metabolic genes, including those involved in butyrate formation, was analyzed using the “shotgun” proteome approach. To date, the bio-based production of 1-butanol, a next-generation biofuel, has relied on several clostridial hosts including C. acetobutylicum and C. beijerinckii. However, these organisms have a low tolerance against 1-butanol even though they are naturally capable of producing it. C. tyrobutyricum cannot produce 1-butanol itself, but has a higher 1-butanol-tolerance and rapid uptake of monosaccharides, compared to those two species. The team identified most of the genes involved in the central metabolism of C. tyrobutyricum from the whole-genome and shotgun proteome data, and this study will accelerate the bacterium’s engineering to produce useful chemicals including butyric acid and 1-butanol, replacing traditional bacterial hosts. Professor Lee said, “The unique metabolic features and energy conservation mechanisms of C. tyrobutyricum can be employed in the various microbial hosts we have previously developed to further improve their productivity and yield. Moreover, findings on C. tyrobutyricum revealed by this study will be the first step to directly engineer this bacterium.” Director Jin-Woo Kim at the Platform Technology Division of the Ministry of Science, ICT and Future Planning of Korea, who oversees the Technology Development Program to Solve Climate Change, said, “Over the years, Professor Lee’s team has researched the development of a bio-refinery system to produce natural and non-natural chemicals with the systems metabolic engineering of microorganisms. They were able to design strategies for the development of diverse industrial microbial strains to produce useful chemicals from inedible biomass-based carbon dioxide fixation. We believe the efficient production of butyric acid using a metabolic engineering approach will play an important role in the establishment of a bioprocess for chemical production.” The title of the research paper is “Deciphering Clostridium tyrobutyricum Metabolism Based on the Who-Genome Sequence and Proteome Analyses.” (DOI: 10.1128/mBio.00743-16) The lead authors are Joungmin Lee, a post-doctoral fellow in the BioProcess Research Center at KAIST, currently working in CJ CheilJedang Research Institute; Yu-Sin Jang, a research fellow in the BioProcess Research Center at KAIST, currently working at Gyeongsang National University as an assistant professor; and Mee-Jung Han, an assistant professor in the Environmental Engineering and Energy Department at Dongyang University. Jin Young Kim, a senior researcher at the Korea Basic Science Institute, also participated in the research. This research was supported by the Technology Development Program to Solve Climate Change’s research project entitled “Systems Metabolic Engineering for Biorefineries” from the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M1A2A2026556). Schematic Diagram of C. tyrobutyricum’s Genome Sequence and Its Proteome Profiles The picture below shows the complete genome sequence, global protein expression profiles, and the genome-based metabolic characteristics during batch fermentation of C. tyrobutyricum.
High Efficiency Bio-butanol production technology developed
KAIST and Korean Company cooperative research team has developed the technology that increases the productivity of bio-butanol to equal that of bio-ethanol and decreases the cost of production. Professor Lee Sang Yeop (Department of Biological-Chemical Engineering) collaborated with GS Caltex and BioFuelChem Ltd. to develop a bio-butanol production process using the system metabolism engineering method that increased the productivity and decreased the production cost. Bio-butanol is being widely regarded as the environmentally friendly next generation energy source that surpasses bio-ethanol. The energy density of bio-butanol is 29.9MJ (mega Joule) per Liter, 48% larger than bio-ethanol (19.6MJ) and comparable to gasoline (32MJ). Bio-butanol is advantageous in that it can be processed from inedible biomass and is therefore unrelated to food crises. Especially because bio-butanol shows similar characteristics especially in its octane rating, enthalpy of vaporization, and air-fuel ratio, it can be used in a gasoline engine. However barriers such as difficulty in gene manipulation of producer bacterium and insufficient information prevented the mass production of bio-butanol. Professor Lee’s team applied the system metabolism engineering method that he had invented to shift the focus to the production pathway of bio-butanol and made a new metabolism model. In the new model the bio-butanol production pathway is divided into the hot channel and the cold channel. The research team focused on improving the efficiency of the hot channel and succeeded in improving the product yield of 49% (compared to theoretical yield) to 87%. The team furthered their research and developed a live bio-butanol collection and removal system with GS Caltex. The collaboration succeeded in producing 585g of butanol using 1.8kg of glucose at a rate of 1.3g per hour, boasting world’s highest concentration, productivity, and rate and improving productivity of fermentation by three fold and decreasing costs by 30%. The result of the research was published in world renowned ‘mBio’ microbiology journal.
Liver Damage Mechanism of Hepatitis C Proven
KAIST researchers found mechanics behind a Hepatitis C virus, thereby taking a step closer to the development of a cure for Hepatitis C. Professor Choi Chul Hui (Department of Biological and Brain Engineering) and Professor Shin Eui Chul (Graduate School of Medical Sciences) proved, for the first time in the world, the mechanism behind liver damage of a patient with Hepatitis C. It is anticipated that this discovery will allow for the development of a Hepatitis C cure that has no side effects and little Liver damage. Hepatitis C is an immune response of the body to the Hepatitis C virus and causes liver irritation. Around 170million people are infected with Hepatitis C worldwide including 1% of the Korean population. Once infected, most cases turn into chronic cases and may lead to liver cancer. However it was impossible to infect Hepatitis C within a test tube cell environment until 2005 and up till then Chimpanzees were used to study the virus which proved to be a huge barrier to research. The research team used cells infected with Hepatitis C virus and found out that the virus works by increasing the destruction of cells by the TNF-a protein responsible for the cell’s immune response. In addition the protein structure of the virus that causes this reaction was successfully found. Conventionally the Hepatitis C medication focused on the suppressing the growth of the virus and therefore had many side effects. The experimental results allow new medication aimed at suppressing the actual mechanism of liver damage to be discovered. The result was selected as the cover dissertation of the September Edition of the Hepatolog magazine.
Prof. Sang-Yup Lee Founding Member of Board of Editors of mBop
Prof. Sang-Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed as one of the founding board of editors of the mBio which will be launched next year, the university reported on Friday (Nov. 20). mBio is the American Society for Microbiology"s first all-online, open access journal which will be launched in next May. According to the mBio website, the journal"s scope "will reflect the enormity of the microbial world, a highly interconnected biosphere where microbes interact with living and non-living matter to produce outcomes that range from symbiosis to pathogenesis, energy acquisition and conversion, climate change, geologic change, food and drug production, and even animal behavioral change." Prof. Lee, LG Chem Chair Professor, is currently the Dean of the College of Life Science and Bioengineering and director of the Center for Systems and Synthetic Biotechnology. He received his B.S. in Chemical Engineering from Seoul National Univeristy in Korea and his M.S. and Ph.D. in Chemical Engineering from Northwestern University. As of September 2009, he has published 298 journal papers and has more than 440 patents either registered or applied. Also, he has published 47 books/book chapters, "Systems Biology and Biotechnology of Escherichia Coli" being the latest. His research interests are systems biology and biotechnology, industrial biotechnology, metabolic engineering, synthetic biology and nanobiotechnology. In particular, he has pioneered systems metabolic engineering, which integrates systems biology with metabolic engineering, for the development of micropoganisms possessing superior properties for industrial applications.
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