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Modular development enables rapid design of media for alternative hosts
  • +2
  • Andrew Biedermann,
  • Isabella Gengaro,
  • Sergio Rodriguez,
  • Kerry Love,
  • John Love
Andrew Biedermann
Massachusetts Institute of Technology
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Isabella Gengaro
Massachusetts Institute of Technology
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Sergio Rodriguez
Massachusetts Institute of Technology
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Kerry Love
Massachusetts Institute of Technology
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John Love
Massachusetts Institute of Technology
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Abstract

Developing media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations of Pichia pastoris as a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.

Peer review status:UNDER REVIEW

06 May 2021Submitted to Biotechnology and Bioengineering
06 May 2021Assigned to Editor
06 May 2021Submission Checks Completed
09 May 2021Reviewer(s) Assigned