A Widespread Radical-Mediated Glycolysis Pathway
Glycyl radical enzymes (GREs) catalyze mechanistically diverse radical-mediated reactions, playing important roles in the metabolism of anaerobic bacteria. The model bacterium <i>Escherichia coli</i> MG1655 contains two GREs of unknown function, YbiW and PflD, which are widespread among human intestinal bacteria. Here, we report that YbiW and PflD catalyze ring-opening C-O cleavage of 1,5-anhydroglucitol-6-phosphate (AG6P) and 1,5-anhydromannitol-6-phosphate (AM6P), respectively. The product of both enzymes, 1-deoxy-fructose-6-phosphate (DF6P), is then cleaved by the aldolases FsaA or FsaB to form glyceraldehyde-3-phosphate (G3P) and hydroxyacetone (HA), which are then reduced by the NADH-dependent dehydrogenase GldA to form 1,2-propanediol (1,2-PDO). Crystal structures of YbiW and PflD in complex with their substrates provided insights into the mechanism of radical-mediated C-O cleavage. This "anhydroglycolysis" pathway enables anaerobic growth of <i>E. coli</i> on 1,5-anhydroglucitol (AG) and 1,5-anhydromannitol (AM), and we probe the feasibility of harnessing this pathway for the production of 1,2-PDO, a highly demanded chiral chemical feedstock, from inexpensive starch. Discovery of the anhydroglycolysis pathway expands the known catalytic repertoire of GREs, clarifies the hitherto unknown physiological functions of the well-studied enzymes FsaA, FsaB, and GldA, and demonstrates how enzyme discovery efforts can cast light on prevalent yet overlooked metabolites in the microbiome.
Authors
- Xinghua Jin (ORCID: https://orcid.org/0000-0002-8883-5234)
- Yiling Hu (ORCID: https://orcid.org/0000-0002-1033-6689)
- Huimin Zhao (ORCID: https://orcid.org/0000-0002-9069-6739)
- Ruoxing Chu
- Shishir Sharma (ORCID: https://orcid.org/0000-0002-7265-3233)
- Kai-Liang Ma
- Wen Shan Yew (ORCID: https://orcid.org/0000-0002-3021-0469)
- Min Hu (ORCID: https://orcid.org/0000-0002-2547-5868)
- Ee Lui Ang (ORCID: https://orcid.org/0000-0002-3070-8056)
- Bo Xue (ORCID: https://orcid.org/0000-0002-5172-2519)
- Tiantian Tao (ORCID: https://orcid.org/0000-0002-4072-4236)
- Robert Robinson (ORCID: https://orcid.org/0000-0001-6367-6903)
- Songgu Wu (ORCID: https://orcid.org/0000-0003-4329-4654)
- Li Jiang (ORCID: https://orcid.org/0000-0002-3551-9430)
- Dazhi Liu (ORCID: https://orcid.org/0000-0003-4621-3207)
- Zhi Li (ORCID: https://orcid.org/0000-0001-6268-0679)
- Yan Zhang (ORCID: https://orcid.org/0000-0003-2031-0631)
- Yanhong Liu (ORCID: https://orcid.org/0000-0002-2246-6974)
- Yan Zhou (ORCID: https://orcid.org/0000-0001-8867-4859)
- Yifeng Wei (ORCID: https://orcid.org/0000-0001-9124-0381)
- Yuchun Zheng
- Yang Tong (ORCID: https://orcid.org/0009-0001-1134-2204)
- Yiwei Chen (ORCID: https://orcid.org/0009-0006-4680-2780)
- Qiaoyu Yang
- Yiren Xie
Institutions
- Agency for Science, Technology and Research (SG)
- Okayama University of Science (JP)
- University of Illinois Urbana-Champaign (US)
- Tianjin University (CN)
- National University of Singapore (SG)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Technical Institute of Physics and Chemistry (CN)
- Vidyasirimedhi Institute of Science and Technology (TH)
- State Key Laboratory of Chemical Engineering (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1021/jacs.4c07718
- Citations
- 6
- Primary Topic
- Microbial Metabolic Engineering and Bioproduction
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Agency for Science, Technology and Research
- National Key Research and Development Program of China
- National Science Fund for Distinguished Young Scholars