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Peer-reviewedCC BY-NC-NDBMC biotechnology

Enhanced production of ε-Poly-L-lysine through overexpression of LysR involved in interspecies interactions.

  • Siying Liao1,2,3
  • Zhanyang Zhang1,2,3
  • Bingxin Chen1,2,3
  • Siyu Tong1,2,3
  • Chen Zhang1,2,3
  • Huawei Zeng1,2,4,3
  • Deyin Zhao2,3
  • Mingtao Zhao2,3
  • Xin Zeng5,6,7,8
  • Bingyue Xin9,10
10 affiliations
  1. 1Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China.
  2. 2Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China.
  3. 3College of Life Sciences, Huaibei Normal University, 100# Dongshan road, Huaibei, Anhui, 235000, P. R. China.
  4. 4Huaibei Key Laboratory for Bio-processing of Agricultural Products, School of Life Sciences, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China.
  5. 5Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China. [email protected].
  6. 6Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China. [email protected].
  7. 7Huaibei Key Laboratory for Bio-processing of Agricultural Products, School of Life Sciences, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China. [email protected].
  8. 8College of Life Sciences, Huaibei Normal University, 100# Dongshan road, Huaibei, Anhui, 235000, P. R. China. [email protected].
  9. 9Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China. [email protected].
  10. 10Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, Huaibei Normal University, Huaibei, Anhui, 235000, P. R. China. [email protected].
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Abstract

Background

Epsilon-poly-L-lysine (ε-PL), an antimicrobial peptide synthesized by Streptomyces albulus through submerged fermentation, is biosynthesized via multiple metabolic pathways. This suggests that global metabolic regulation and interspecies interactions contribute significantly to enhancing ε-PL yield. Current genetic and metabolic engineering strategies, however, primarily aim at strengthening specific metabolic fluxes, without adequately coordinating the diverse physiological requirements involved in ε-PL production. Previous research has shown that interspecies stress induced by Streptomyces gilvosporeus can elicit a broad enhancement of ε-PL biosynthetic pathways. Building on this finding, the present study seeks to identify key transcriptional regulators that respond to such interspecies stress and are capable of systematically improving metabolic efficiency.Results

Comparative transcriptomic analysis revealed that transcription factors from the RegX3, LysR, and TetR families were significantly upregulated in S. albulus under interspecies stress. Corresponding overexpression strains (OE-RegX3, OE-LysR, OE-TetR1, and OE-TetR2) were constructed using a one-step cloning strategy, all exhibiting altered colony morphology. Among them, OE-LysR showed a 60.9% increase in ε-PL production compared to the wild type in flask cultures. When scaled to a 5-L bioreacter and stimulated with S. gilvosporeus live cells, the ε-PL titer of OE-LysR further rose to 39.6 g/L, marking a 51.1% improvement. Physiological analyses revealed that the enhanced ε-PL production was attributed to the upregulation of key biosynthetic and metabolic pathways.Conclusions

LysR was identified as a key regulator that mediates interspecies stress from S. gilvosporeus to enhance ε-PL biosynthesis in S. albulus. Overexpression of LysR globally activated ε-PL-related metabolic pathways and markedly increased ε-PL production at both flask and fermenter scales, especially when combined with S. gilvosporeus stimulation. These findings offer new strategies for harnessing interspecies stress to enhance antibiotic fermentation efficiency.

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Cite

BibTeXRIS
BibTeX
@article{liao2026enhanced,
  title = {{Enhanced production of ε-Poly-L-lysine through overexpression of LysR involved in interspecies interactions.}},
  author = {Siying Liao and Zhanyang Zhang and Bingxin Chen and Siyu Tong and Chen Zhang and Huawei Zeng and Deyin Zhao and Mingtao Zhao and Xin Zeng and Bingyue Xin},
  journal = {BMC biotechnology},
  year = {2026},
  month = aug,
  doi = {10.1186/s12896-026-01208-z},
  url = {https://europepmc.org/article/MED/42958265},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Enhanced production of ε-Poly-L-lysine through overexpression of LysR involved in interspecies interactions.
AU  - Siying Liao
AU  - Zhanyang Zhang
AU  - Bingxin Chen
AU  - Siyu Tong
AU  - Chen Zhang
AU  - Huawei Zeng
AU  - Deyin Zhao
AU  - Mingtao Zhao
AU  - Xin Zeng
AU  - Bingyue Xin
PY  - 2026
DA  - 2026/08/01
JO  - BMC biotechnology
DO  - 10.1186/s12896-026-01208-z
UR  - https://europepmc.org/article/MED/42958265
AB  - Background  Epsilon-poly-L-lysine (ε-PL), an antimicrobial peptide synthesized by Streptomyces albulus through submerged fermentation, is biosynthesized via multiple metabolic pathways. This suggests that global metabolic regulation and interspecies interactions contribute significantly to enhancing ε-PL yield. Current genetic and metabolic engineering strategies, however, primarily aim at strengthening specific metabolic fluxes, without adequately coordinating the diverse physiological requirements involved in ε-PL production. Previous research has shown that interspecies stress induced by Streptomyces gilvosporeus can elicit a broad enhancement of ε-PL biosynthetic pathways. Building on this finding, the present study seeks to identify key transcriptional regulators that respond to such interspecies stress and are capable of systematically improving metabolic efficiency.Results  Comparative transcriptomic analysis revealed that transcription factors from the RegX3, LysR, and TetR families were significantly upregulated in S. albulus under interspecies stress. Corresponding overexpression strains (OE-RegX3, OE-LysR, OE-TetR1, and OE-TetR2) were constructed using a one-step cloning strategy, all exhibiting altered colony morphology. Among them, OE-LysR showed a 60.9% increase in ε-PL production compared to the wild type in flask cultures. When scaled to a 5-L bioreacter and stimulated with S. gilvosporeus live cells, the ε-PL titer of OE-LysR further rose to 39.6 g/L, marking a 51.1% improvement. Physiological analyses revealed that the enhanced ε-PL production was attributed to the upregulation of key biosynthetic and metabolic pathways.Conclusions  LysR was identified as a key regulator that mediates interspecies stress from S. gilvosporeus to enhance ε-PL biosynthesis in S. albulus. Overexpression of LysR globally activated ε-PL-related metabolic pathways and markedly increased ε-PL production at both flask and fermenter scales, especially when combined with S. gilvosporeus stimulation. These findings offer new strategies for harnessing interspecies stress to enhance antibiotic fermentation efficiency.
SN  - 1472-6750
ER  -