Improving the performance of solventogenic clostridia by reinforcing the biotin synthetic pathway |
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| Institution: | 1. Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, China;1. Vascular Biology Program, Boston Children’s Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA;1. Department of Environmental Engineering, National ILan University, Yilan 260, Taiwan;2. Energy Technology Research Center, Department of Civil Engineering, Faculty of Engineering, Prince of Songkla University, Hat Yai Campus, Hat Yai, Songkhla 90110, Thailand;1. MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu, 210095, PR China;2. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA;3. Department of Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA |
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| Abstract: | An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of solventogenic clostridia, we revealed that the insufficient biosynthesis of biotin, a pivotal coenzyme for many important biological processes, is a major limiting bottleneck in this anaerobe’s performance. To address this problem, we strengthened the biotin synthesis of C. acetobutylicum by overexpressing four relevant genes involved in biotin transport and biosynthesis. This strategy led to faster growth and improved the titer and productivity of acetone, butanol and ethanol (ABE solvents) of C. acetobutylicum in both biotin-containing and biotin-free media. Expressionally modulating these four genes by modifying the ribosome binding site further promoted cellular performance, achieving ABE solvent titer and productivity as high as 21.9 g/L and 0.30 g/L/h, respectively, in biotin-free medium; these values exceeded those of the wild-type strain by over 30%. More importantly, biotin synthesis reinforcement also conferred improved ability of C. acetobutylicum to use hexose and pentose sugars, further demonstrating the potential of this metabolic-engineering strategy in solventogenic clostridia. |
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| Keywords: | Engineering robust clostridia Biotin synthesis reinforcement Solvent titer and productivity |
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