High-throughput optofluidic screening for improved microbial cell factories via real-time micron-scale productivity monitoring.
Lab Chip
; 21(15): 2901-2912, 2021 08 07.
Article
en En
| MEDLINE
| ID: mdl-34160512
The industrial synthetic biology sector has made huge investments to achieve relevant miniaturized screening systems for scalable fermentation. Here we present the first example of a high-throughput (>103 genotypes per week) perfusion-based screening system to improve small-molecule secretion from microbial strains. Using the Berkeley Lights Beacon® system, the productivity of each strain could be directly monitored in real time during continuous culture, yielding phenotypes that correlated strongly (r2 > 0.8, p < 0.0005) with behavior in industrially relevant bioreactor processes. This method allows a much closer approximation of a typical fed-batch fermentation than conventional batch-like droplet or microplate culture models, in addition to rich time-dependent data on growth and productivity. We demonstrate these advantages by application to the improvement of high-productivity strains using whole-genome random mutagenesis, yielding mutants with substantially improved (by up to 85%) peak specific productivities in bioreactors. Each screen of â¼5 × 103 mutants could be completed in under 8 days (including 5 days involving user intervention), saving â¼50-75% of the time required for conventional microplate-based screening methods.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Reactores Biológicos
/
Ensayos Analíticos de Alto Rendimiento
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Idioma:
En
Revista:
Lab Chip
Asunto de la revista:
BIOTECNOLOGIA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido