In silico metabolic engineering of Clostridium ljungdahlii for synthesis gas fermentation |
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| Affiliation: | 1. School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510006, PR China;2. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA;3. Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA;1. Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Songling Road 189, Qingdao 266101, China;2. University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing 100049, China;1. School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea;2. Bioenergy & Environmental Sustainable Technology (BEST) Research Group, Department of Chemical Engineering, COMSATS University Islamabad (CUI), Lahore Campus, Defense Road, Off Raiwind Road, Lahore, Pakistan;1. TERI University, 10 Institutional Area, Vasant Kunj, New Delhi 110 070, India;2. TERI, Darbari Seth Block, India Habitat Centre, New Delhi 110 003, India;1. Department of Biological and Environmental Engineering, Cornell University, Riley-Robb Hall, Ithaca, NY 14853, United States;2. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Queensland 4072, Australia;3. University of Tübingen, Center for Applied GeoSciences, Hölderlinstr. 12, 72074 Tübingen, Germany |
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| Abstract: | Synthesis gas fermentation is one of the most promising routes to convert synthesis gas (syngas; mainly comprised of H2 and CO) to renewable liquid fuels and chemicals by specialized bacteria. The most commonly studied syngas fermenting bacterium is Clostridium ljungdahlii, which produces acetate and ethanol as its primary metabolic byproducts. Engineering of C. ljungdahlii metabolism to overproduce ethanol, enhance the synthesize of the native byproducts lactate and 2,3-butanediol, and introduce the synthesis of non-native products such as butanol and butyrate has substantial commercial value. We performed in silico metabolic engineering studies using a genome-scale reconstruction of C. ljungdahlii metabolism and the OptKnock computational framework to identify gene knockouts that were predicted to enhance the synthesis of these native products and non-native products, introduced through insertion of the necessary heterologous pathways. The OptKnock derived strategies were often difficult to assess because increase product synthesis was invariably accompanied by decreased growth. Therefore, the OptKnock strategies were further evaluated using a spatiotemporal metabolic model of a syngas bubble column reactor, a popular technology for large-scale gas fermentation. Unlike flux balance analysis, the bubble column model accounted for the complex tradeoffs between increased product synthesis and reduced growth rates of engineered mutants within the spatially varying column environment. The two-stage methodology for deriving and evaluating metabolic engineering strategies was shown to yield new C. ljungdahlii gene targets that offer the potential for increased product synthesis under realistic syngas fermentation conditions. |
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| Keywords: | Gas fermentation OptKnock Spatiotemporal metabolic modeling |
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