IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03232-w.html
   My bibliography  Save this article

Diverse genetic error modes constrain large-scale bio-based production

Author

Listed:
  • Peter Rugbjerg

    (Technical University of Denmark)

  • Nils Myling-Petersen

    (Technical University of Denmark)

  • Andreas Porse

    (Technical University of Denmark)

  • Kira Sarup-Lytzen

    (Technical University of Denmark)

  • Morten O. A. Sommer

    (Technical University of Denmark)

Abstract

A transition toward sustainable bio-based chemical production is important for green growth. However, productivity and yield frequently decrease as large-scale microbial fermentation progresses, commonly ascribed to phenotypic variation. Yet, given the high metabolic burden and toxicities, evolutionary processes may also constrain bio-based production. We experimentally simulate large-scale fermentation with mevalonic acid-producing Escherichia coli. By tracking growth rate and production, we uncover how populations fully sacrifice production to gain fitness within 70 generations. Using ultra-deep (>1000×) time-lapse sequencing of the pathway populations, we identify multiple recurring intra-pathway genetic error modes. This genetic heterogeneity is only detected using deep-sequencing and new population-level bioinformatics, suggesting that the problem is underestimated. A quantitative model explains the population dynamics based on enrichment of spontaneous mutant cells. We validate our model by tuning production load and escape rate of the production host and apply multiple orthogonal strategies for postponing genetically driven production declines.

Suggested Citation

  • Peter Rugbjerg & Nils Myling-Petersen & Andreas Porse & Kira Sarup-Lytzen & Morten O. A. Sommer, 2018. "Diverse genetic error modes constrain large-scale bio-based production," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03232-w
    DOI: 10.1038/s41467-018-03232-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03232-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-018-03232-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Linxia Liu & Jinlong Li & Yuanming Gai & Zhizhong Tian & Yanyan Wang & Tenghe Wang & Pi Liu & Qianqian Yuan & Hongwu Ma & Sang Yup Lee & Dawei Zhang, 2023. "Protein engineering and iterative multimodule optimization for vitamin B6 production in Escherichia coli," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. François Bertaux & Sebastián Sosa-Carrillo & Viktoriia Gross & Achille Fraisse & Chetan Aditya & Mariela Furstenheim & Gregory Batt, 2022. "Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Duncan Ingram & Guy-Bart Stan, 2023. "Modelling genetic stability in engineered cell populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Alex J. H. Fedorec & Neythen J. Treloar & Ke Yan Wen & Linda Dekker & Qing Hsuan Ong & Gabija Jurkeviciute & Enbo Lyu & Jack W. Rutter & Kathleen J. Y. Zhang & Luca Rosa & Alexey Zaikin & Chris P. Bar, 2024. "Emergent digital bio-computation through spatial diffusion and engineered bacteria," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Noor Radde & Genevieve A. Mortensen & Diya Bhat & Shireen Shah & Joseph J. Clements & Sean P. Leonard & Matthew J. McGuffie & Dennis M. Mishler & Jeffrey E. Barrick, 2024. "Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03232-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.