Microbial synthesis of sedoheptulose from glucose by metabolically engineered Corynebacterium glutamicum.

Publisher: BioMed Central Country of Publication: England NLM ID: 101139812 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2859 (Electronic) Linking ISSN: 14752859 NLM ISO Abbreviation: Microb Cell Fact Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Corynebacterium glutamicum*/metabolism ; Corynebacterium glutamicum*/genetics ; Corynebacterium glutamicum*/enzymology ; Metabolic Engineering*/methods ; Heptoses*/biosynthesis ; Heptoses*/metabolism ; Glucose*/metabolism; Pentose Phosphate Pathway ; Fermentation

Background: Seven-carbon sugars, which rarely exist in nature, are the key constitutional unit of septacidin and hygromycin B in bacteria. These sugars exhibit a potential therapeutic effect for hypoglycaemia and cancer and serve as building blocks for the synthesis of C-glycosides and novel antibiotics. However, chemical and enzymatic approaches for the synthesis of seven-carbon sugars have faced challenges, such as complex reaction steps, low overall yields and high-cost feedstock, limiting their industrial-scale production.
Results: In this work, we propose a strain engineering approach for synthesising sedoheptulose using glucose as sole feedstock. The gene pfkA encoding 6-phosphofructokinase in Corynebacterium glutamicum was inactivated to direct the carbon flux towards the pentose phosphate pathway in the cellular metabolic network. This genetic modification successfully enabled the synthesis of sedoheptulose from glucose. Additionally, we identified key enzymes responsible for product formation through transcriptome analysis, and their corresponding genes were overexpressed, resulting in a further 20% increase in sedoheptulose production.
Conclusion: We achieved a sedoheptulose concentration of 24 g/L with a yield of 0.4 g/g glucose in a 1 L fermenter, marking the highest value up to date. The produced sedoheptulose could further function as feedstock for synthesising structural seven-carbon sugars through coupling with enzymatic isomerisation, epimerisation and reduction reactions.
(© 2024. The Author(s).)

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TSBICIP-KJGG-008-03 and TSBICIP-PTJJ-007-10 Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project; TSBICIP-KJGG-008-03 and TSBICIP-PTJJ-007-10 Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project; TSBICIP-KJGG-008-03 and TSBICIP-PTJJ-007-10 Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project; TSBICIP-KJGG-008-03 and TSBICIP-PTJJ-007-10 Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project; No. 32271545 China National Key Research and Development; No. 32271545 China National Key Research and Development; No. 32271545 China National Key Research and Development; No. 32271545 Natural Science Foundation of China; No. 32271545 Natural Science Foundation of China; No. 32271545 Natural Science Foundation of China; 2021176 Youth Promotion Association of Chinese Academy of Sciences; 2021176 Youth Promotion Association of Chinese Academy of Sciences; 2021176 Youth Promotion Association of Chinese Academy of Sciences; JZ1-ZG2-2301-026 TIB Competitive Research Project; JZ1-ZG2-2301-026 TIB Competitive Research Project; JZ1-ZG2-2301-026 TIB Competitive Research Project

Keywords: Corynebacterium glutamicum; Metabolic engineering; Sedoheptulose; Seven-carbon sugars

0 (Heptoses)
IY9XDZ35W2 (Glucose)
3019-74-7 (sedoheptulose)

Date Created: 20240913 Date Completed: 20240914 Latest Revision: 20240916

20250114

PMC11401394

10.1186/s12934-024-02501-2

39272184