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A synthetic methylotroph achieves accelerated cell growth by alleviating transcription-replication conflicts

Author

Listed:
  • Xin Meng

    (Jiangnan University)

  • Guipeng Hu

    (Jiangnan University)

  • Xiaomin Li

    (Jiangnan University)

  • Cong Gao

    (Jiangnan University)

  • Wei Song

    (Jiangnan University)

  • Wanqing Wei

    (Jiangnan University)

  • Jing Wu

    (Jiangnan University)

  • Liming Liu

    (Jiangnan University)

Abstract

Microbial utilization of methanol for valorization is an effective way to advance green bio-manufacturing technology. Although synthetic methylotrophs have been developed, strategies to enhance their cell growth rate and internal regulatory mechanism remain underexplored. In this study, we design a synthetic methanol assimilation (SMA) pathway containing only six enzymes linked to central carbon metabolism, which does not require energy and carbon emissions. Through rational design and laboratory evolution, E. coli harboring with the SMA pathway is converted into a synthetic methylotroph. By self-adjusting the expression of TOPAI (topoisomerase I inhibitor) to alleviate transcriptional-replication conflicts (TRCs), the doubling time of methylotrophic E. coli is reduced to 4.5 h, approaching that of natural methylotrophs. This work has the potential to overcome the growth limitation of C1-assimilating microbes and advance the development of a circular carbon economy.

Suggested Citation

  • Xin Meng & Guipeng Hu & Xiaomin Li & Cong Gao & Wei Song & Wanqing Wei & Jing Wu & Liming Liu, 2025. "A synthetic methylotroph achieves accelerated cell growth by alleviating transcription-replication conflicts," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55502-5
    DOI: 10.1038/s41467-024-55502-5
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    References listed on IDEAS

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    1. Fabian Meyer & Philipp Keller & Johannes Hartl & Olivier G. Gröninger & Patrick Kiefer & Julia A. Vorholt, 2018. "Methanol-essential growth of Escherichia coli," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Philipp Keller & Elad Noor & Fabian Meyer & Michael A. Reiter & Stanislav Anastassov & Patrick Kiefer & Julia A. Vorholt, 2020. "Methanol-dependent Escherichia coli strains with a complete ribulose monophosphate cycle," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Monica I. Espinosa & Ricardo A. Gonzalez-Garcia & Kaspar Valgepea & Manuel R. Plan & Colin Scott & Isak S. Pretorius & Esteban Marcellin & Ian T. Paulsen & Thomas C. Williams, 2020. "Adaptive laboratory evolution of native methanol assimilation in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    4. Liang-Yu Nieh & Frederic Y.-H. Chen & Hsin-Wei Jung & Kuan-Yu Su & Chao-Yin Tsuei & Chun-Ting Lin & Yue-Qi Lee & James C. Liao, 2024. "Evolutionary engineering of methylotrophic E. coli enables fast growth on methanol," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Charles Bou-Nader & Ankur Bothra & David N. Garboczi & Stephen H. Leppla & Jinwei Zhang, 2022. "Structural basis of R-loop recognition by the S9.6 monoclonal antibody," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Philipp Keller & Michael A. Reiter & Patrick Kiefer & Thomas Gassler & Lucas Hemmerle & Philipp Christen & Elad Noor & Julia A. Vorholt, 2022. "Generation of an Escherichia coli strain growing on methanol via the ribulose monophosphate cycle," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Benjamin M. Woolston & Jason R. King & Michael Reiter & Bob Van Hove & Gregory Stephanopoulos, 2018. "Improving formaldehyde consumption drives methanol assimilation in engineered E. coli," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    8. Yuko Fujioka & Jahangir Md. Alam & Daisuke Noshiro & Kazunari Mouri & Toshio Ando & Yasushi Okada & Alexander I. May & Roland L. Knorr & Kuninori Suzuki & Yoshinori Ohsumi & Nobuo N. Noda, 2020. "Phase separation organizes the site of autophagosome formation," Nature, Nature, vol. 578(7794), pages 301-305, February.
    9. Hui Liu & Pei Zhou & Mengya Qi & Liang Guo & Cong Gao & Guipeng Hu & Wei Song & Jing Wu & Xiulai Chen & Jian Chen & Wei Chen & Liming Liu, 2022. "Enhancing biofuels production by engineering the actin cytoskeleton in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Hong Yu & James C. Liao, 2018. "A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    11. Musa, S. Danlami & Zhonghua, Tang & Ibrahim, Abdullateef O. & Habib, Mukhtar, 2018. "China's energy status: A critical look at fossils and renewable options," Renewable and Sustainable Energy Reviews, Elsevier, vol. 81(P2), pages 2281-2290.
    12. Dmitry Sutormin & Alina Galivondzhyan & Olga Musharova & Dmitrii Travin & Anastasiia Rusanova & Kseniya Obraztsova & Sergei Borukhov & Konstantin Severinov, 2022. "Interaction between transcribing RNA polymerase and topoisomerase I prevents R-loop formation in E. coli," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
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