Modular development enables rapid design of media for alternative hosts.

Autor: Biedermann AM; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Gengaro IR; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Rodriguez-Aponte SA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Love KR; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Love JC; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2022 Jan; Vol. 119 (1), pp. 59-71. Date of Electronic Publication: 2021 Oct 18.
DOI: 10.1002/bit.27947
Abstrakt: 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.
(© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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