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PreprintCC BY-NC-NDbioRxiv

Adaptive laboratory evolution of a yeast co-culture chassis for modular bioproduction

  1. 1Department of Bioengineering, Imperial College London

Abstract

Synthetic microbial consortia have the potential to bring novel architectures to biotechnological processes. They enable more flexible and efficient bioprocesses by reducing metabolic burden and supporting division of labour. Obligately mutualistic cross-feeding has been used to stabilise the population composition of artificially assembled consortia. However, many current strategies rely on the cross-feeding of metabolites with limited exchange rates, and this imposes a growth burden on the consortium members. Here, we used adaptive laboratory evolution (ALE) to address this growth bottleneck and create an optimised co-culture chassis to host bioproduction functions. Transcriptome analysis revealed how ALE alleviated stress responses associated with nutritional restrictions in the non-evolved cross-feeding system. Using a case-study split bioproduction pathway, we demonstrated that improvements in the chassis growth performance resulted in production improvements, surpassing the performance of a monoculture implementation by 1.5-fold. Our results show the potential of ALE to optimise the cross-feeding layer of yeast co-cultures, and how this enables the efficient implementation of a bioproduction process.

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BibTeX
@misc{ruizsanchis2026adaptive,
  title = {{Adaptive laboratory evolution of a yeast co-culture chassis for modular bioproduction}},
  author = {D. Ruiz-Sanchis and J. Lopez-Salinas and C. Klemm and M. Gallego Garcia and R. Ledesma-Amaro},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.06.747466},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.06.747466v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Adaptive laboratory evolution of a yeast co-culture chassis for modular bioproduction
AU  - D. Ruiz-Sanchis
AU  - J. Lopez-Salinas
AU  - C. Klemm
AU  - M. Gallego Garcia
AU  - R. Ledesma-Amaro
PY  - 2026
DA  - 2026/09/06
PB  - bioRxiv
DO  - 10.64898/2026.09.06.747466
UR  - https://www.biorxiv.org/content/10.64898/2026.09.06.747466v1
AB  - Synthetic microbial consortia have the potential to bring novel architectures to biotechnological processes. They enable more flexible and efficient bioprocesses by reducing metabolic burden and supporting division of labour. Obligately mutualistic cross-feeding has been used to stabilise the population composition of artificially assembled consortia. However, many current strategies rely on the cross-feeding of metabolites with limited exchange rates, and this imposes a growth burden on the consortium members. Here, we used adaptive laboratory evolution (ALE) to address this growth bottleneck and create an optimised co-culture chassis to host bioproduction functions. Transcriptome analysis revealed how ALE alleviated stress responses associated with nutritional restrictions in the non-evolved cross-feeding system. Using a case-study split bioproduction pathway, we demonstrated that improvements in the chassis growth performance resulted in production improvements, surpassing the performance of a monoculture implementation by 1.5-fold. Our results show the potential of ALE to optimise the cross-feeding layer of yeast co-cultures, and how this enables the efficient implementation of a bioproduction process.
ER  -