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Peer-reviewedCC BYJournal of agricultural and food chemistry

Biosynthesis of 3-Hydroxy-3-methylbutyrate by Probiotic Escherichia coli Nissle 1917.

  • Jenny Ji-Chan Hung1
  • Tina Wen-Ting Shih2
  • Alice Pin-Yi Du3
  • Ethan I Lan2,3
  1. 1Ph.D. Degree Program of Biomedical Science and Engineering, , National Yang Ming Chiao Tung University, Hsinchu City300, Taiwan.
  2. 2Institute of Molecular Medicine and Bioengineering, , National Yang Ming Chiao Tung University, Hsinchu City300, Taiwan.
  3. 3Department of Biological Science and Technology, , National Yang Ming Chiao Tung University, Hsinchu City300, Taiwan.
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Abstract

3-Hydroxy-3-methylbutyrate (HMB) is an important nutritional supplement for managing sarcopenia. This study engineered an HMB biosynthetic pathway in the probiotic Escherichia coli Nissle 1917 (EcN). The initial engineered strain exhibited low HMB titers, as carbon flux was primarily diverted toward acetate formation. Deleting the pyruvate oxidase gene (poxB) reduced acetate but caused significant pyruvate accumulation, revealing a severe kinetic bottleneck in endogenous pyruvate dehydrogenase (PDH) activity. Supplementing pantothenic acid (Vitamin B5) profoundly expanded the intracellular coenzyme A (CoA) pool, providing the essential backbone for pathway intermediates. This strategy enhanced PDH flux and improved HMB production by 5.5-fold. Through fed-batch fermentation, the engineered strain achieved an HMB titer of 8.6 g/L with a yield of 0.14 g/g glucose. The results of this study provided a probiotic strain that can synthesize HMB de novo and demonstrated the importance of pantothenic acid availability for EcN metabolic engineering.

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Cite

BibTeXRIS
BibTeX
@article{hung2026biosynthesis,
  title = {{Biosynthesis of 3-Hydroxy-3-methylbutyrate by Probiotic Escherichia coli Nissle 1917.}},
  author = {Jenny Ji-Chan Hung and Tina Wen-Ting Shih and Alice Pin-Yi Du and Ethan I Lan},
  journal = {Journal of agricultural and food chemistry},
  year = {2026},
  month = sep,
  doi = {10.1021/acs.jafc.6c08735},
  url = {https://europepmc.org/article/MED/42916519},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Biosynthesis of 3-Hydroxy-3-methylbutyrate by Probiotic Escherichia coli Nissle 1917.
AU  - Jenny Ji-Chan Hung
AU  - Tina Wen-Ting Shih
AU  - Alice Pin-Yi Du
AU  - Ethan I Lan
PY  - 2026
DA  - 2026/09/01
JO  - Journal of agricultural and food chemistry
DO  - 10.1021/acs.jafc.6c08735
UR  - https://europepmc.org/article/MED/42916519
AB  - 3-Hydroxy-3-methylbutyrate (HMB) is an important nutritional supplement for managing sarcopenia. This study engineered an HMB biosynthetic pathway in the probiotic Escherichia coli Nissle 1917 (EcN). The initial engineered strain exhibited low HMB titers, as carbon flux was primarily diverted toward acetate formation. Deleting the pyruvate oxidase gene (poxB) reduced acetate but caused significant pyruvate accumulation, revealing a severe kinetic bottleneck in endogenous pyruvate dehydrogenase (PDH) activity. Supplementing pantothenic acid (Vitamin B5) profoundly expanded the intracellular coenzyme A (CoA) pool, providing the essential backbone for pathway intermediates. This strategy enhanced PDH flux and improved HMB production by 5.5-fold. Through fed-batch fermentation, the engineered strain achieved an HMB titer of 8.6 g/L with a yield of 0.14 g/g glucose. The results of this study provided a probiotic strain that can synthesize HMB de novo and demonstrated the importance of pantothenic acid availability for EcN metabolic engineering.
SN  - 0021-8561
SN  - 1520-5118
ER  -