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Peer-reviewedCC BY-NC-ND 4.0Nature Communications

ATHENA: a dynamic metabolic hub balancing carbon economy and energy supply in microbial synthesis

  • Likun Guo1
  • Xinjun Feng2
  • Xingyu Zhang1
  • Chao Xu3
  • Wei Liu4
  • Yujia Bi1
  • Qingsheng Qi1
  • Mo Xian3
  • Guang Zhao1
4 affiliations
  1. 1State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China
  2. 2Research Center of Advanced Biological Manufacture, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
  3. 3CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, China
  4. 4Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou, China
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Abstract

Diverse chemicals biosynthesis demand distinct precursor acetyl-CoA and energy inputs, yet strategies balancing carbon atom economy and energy generation for varied products remain scarce. Here, we design an autonomous hybrid energy-carbon balancing apparatus (ATHENA) to establish a paradigm for redox-driven, dynamically adaptive regulation of carbon conservation and energy synthesis in Escherichia coli. ATHENA features modularization of acetyl-CoA and NADH synthesis pathways for carbon conservation and energy generation, paired with NADH-responsive positive and negative genetic circuits constructed using the BsRex sensor and antisense RNA. This system enables intracellular redox state-dependent rational metabolic flux allocation to balance carbon atom economy and energy generation. Ultimately, ATHENA significantly improves yields and titers of five products with differential acetyl-CoA and energy demands. In the 5-L bioreactor, acetate yield markedly exceeds its native theoretical yield, while that of mevalonate nearly approaches this theoretical upper limit. This work provides a universal strategy for constructing high carbon-yield microbial chassis cells.

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Cite

BibTeXRIS
BibTeX
@article{guo2026athena,
  title = {{ATHENA: a dynamic metabolic hub balancing carbon economy and energy supply in microbial synthesis}},
  author = {Likun Guo and Xinjun Feng and Xingyu Zhang and Chao Xu and Wei Liu and Yujia Bi and Qingsheng Qi and Mo Xian and Guang Zhao},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-78191-8},
  url = {https://doi.org/10.1038/s41467-026-78191-8},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - ATHENA: a dynamic metabolic hub balancing carbon economy and energy supply in microbial synthesis
AU  - Likun Guo
AU  - Xinjun Feng
AU  - Xingyu Zhang
AU  - Chao Xu
AU  - Wei Liu
AU  - Yujia Bi
AU  - Qingsheng Qi
AU  - Mo Xian
AU  - Guang Zhao
PY  - 2026
DA  - 2026/09/25
JO  - Nature Communications
DO  - 10.1038/s41467-026-78191-8
UR  - https://doi.org/10.1038/s41467-026-78191-8
AB  - Diverse chemicals biosynthesis demand distinct precursor acetyl-CoA and energy inputs, yet strategies balancing carbon atom economy and energy generation for varied products remain scarce. Here, we design an autonomous hybrid energy-carbon balancing apparatus (ATHENA) to establish a paradigm for redox-driven, dynamically adaptive regulation of carbon conservation and energy synthesis in Escherichia coli. ATHENA features modularization of acetyl-CoA and NADH synthesis pathways for carbon conservation and energy generation, paired with NADH-responsive positive and negative genetic circuits constructed using the BsRex sensor and antisense RNA. This system enables intracellular redox state-dependent rational metabolic flux allocation to balance carbon atom economy and energy generation. Ultimately, ATHENA significantly improves yields and titers of five products with differential acetyl-CoA and energy demands. In the 5-L bioreactor, acetate yield markedly exceeds its native theoretical yield, while that of mevalonate nearly approaches this theoretical upper limit. This work provides a universal strategy for constructing high carbon-yield microbial chassis cells.
SN  - 2041-1723
ER  -