The future of self-selecting and stable fermentations
Reviewartikel, 2020

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.

Phenotypic heterogeneity

Evolutionary stability

Production stability

Production robustness

Metabolic burden

Genetic heterogeneity

Production load

Författare

Peter Rugbjerg

Chalmers, Biologi och bioteknik, Industriell bioteknik

Lisbeth Olsson

Chalmers, Biologi och bioteknik, Industriell bioteknik

Journal of Industrial Microbiology and Biotechnology

1367-5435 (ISSN) 1476-5535 (eISSN)

Vol. In Press

Ämneskategorier

Biomedicinsk laboratorievetenskap/teknologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Annan industriell bioteknik

DOI

10.1007/s10295-020-02325-0

PubMed

33136197

Mer information

Senast uppdaterat

2020-12-03