The future of self-selecting and stable fermentations.
J Ind Microbiol Biotechnol
; 47(11): 993-1004, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-33136197
ABSTRACT
Unfavorable cell heterogeneity is a frequent risk during bioprocess scale-up and characterized by rising frequencies of low-producing cells. Low-producing cells emerge by both non-genetic and genetic variation and will enrich due to their higher specific growth rate during the extended number of cell divisions of large-scale bioproduction. Here, we discuss recent strategies for synthetic stabilization of fermentation populations and argue for their application to make cell factory designs that better suit industrial needs. Genotype-directed strategies leverage DNA-sequencing data to inform strain design. Self-selecting phenotype-directed strategies couple high production with cell proliferation, either by redirected metabolic pathways or synthetic product biosensing to enrich for high-performing cell variants. Evaluating production stability early in new cell factory projects will guide heterogeneity-reducing design choices. As good initial metrics, we propose production half-life from standardized serial-passage stability screens and production load, quantified as production-associated percent-wise growth rate reduction. Incorporating more stable genetic designs will greatly increase scalability of future cell factories through sustaining a high-production phenotype and enabling stable long-term production.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fermentación
/
Ingeniería Metabólica
Idioma:
En
Año:
2020
Tipo del documento:
Article