Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in .
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| Main Authors: | , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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Synthetic and systems biotechnology
2026
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| _version_ | 1868266082217754624 |
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| author | Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun |
| author_facet | Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun |
| collection | PubMed - marine biology |
| contents | Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in . Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun Succinic acid, an essential platform chemical with extensive utility in biodegradable materials, pharmaceuticals, and the food industry, faces challenges of high energy consumption and environmental pollution in traditional chemical synthesis. Here, we employed multiplex metabolic engineering and adaptive laboratory evolution to enhance succinic acid biosynthesis in . By attenuating succinate dehydrogenase (Sdh) activity, mitigating by-product accumulation, and enhancing the succinate synthesis pathway, engineered strains showed efficient succinic acid production from glycerol. The titer reached 130.99 g/L under unregulated pH conditions, translating to a yield of 0.35 g/g and a productivity of 0.70 g/(L·h). Subsequently, transporter engineering and adaptive evolution strategies were applied to enhance glucose utilization for succinic acid synthesis, yielding an evolved strain that eliminated the growth lag phase and produced 106.68 g/L succinic acid from glucose, which translated to a yield of 0.32 g/g and a productivity of 0.64 g/(L·h). Additionally, transcriptomic analysis and inverse metabolic engineering revealed that 4-hydroxyphenylpyruvate dioxygenase (4-Hppd) in the tyrosine degradation pathway partially restored the growth of Sdh-deficient strains on glucose, offering new insights for subsequent succinic acid biomanufacturing using . . |
| format | Artículo científico |
| id | pubmed_41725899 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Synthetic and systems biotechnology |
| record_format | pubmed |
| spellingShingle | Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in . Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in . Sun, Tao Sun, Mei-Li Lin, Lu Gao, Jian Ledesma-Amaro, Rodrigo Wang, Kaifeng Ji, Xiao-Jun Succinic acid, an essential platform chemical with extensive utility in biodegradable materials, pharmaceuticals, and the food industry, faces challenges of high energy consumption and environmental pollution in traditional chemical synthesis. Here, we employed multiplex metabolic engineering and adaptive laboratory evolution to enhance succinic acid biosynthesis in . By attenuating succinate dehydrogenase (Sdh) activity, mitigating by-product accumulation, and enhancing the succinate synthesis pathway, engineered strains showed efficient succinic acid production from glycerol. The titer reached 130.99 g/L under unregulated pH conditions, translating to a yield of 0.35 g/g and a productivity of 0.70 g/(L·h). Subsequently, transporter engineering and adaptive evolution strategies were applied to enhance glucose utilization for succinic acid synthesis, yielding an evolved strain that eliminated the growth lag phase and produced 106.68 g/L succinic acid from glucose, which translated to a yield of 0.32 g/g and a productivity of 0.64 g/(L·h). Additionally, transcriptomic analysis and inverse metabolic engineering revealed that 4-hydroxyphenylpyruvate dioxygenase (4-Hppd) in the tyrosine degradation pathway partially restored the growth of Sdh-deficient strains on glucose, offering new insights for subsequent succinic acid biomanufacturing using . . |
| title | Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in . |
| url | https://pubmed.ncbi.nlm.nih.gov/41725899/ |