Staying productive under pressure: systems evaluations of β-carotene production in Yarrowia lipolytica under continuous fermentation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Scaling biomanufacturing from laboratory to industrial scale poses significant challenges, especially for continuous fermentation. This study investigates these challenges using a β-carotene-producing Yarrowia lipolytica strain. Through fermentation experiments and proteomics, we have assessed how fermentation modes, carbon sources, dissolved O2, and media composition influence long-term bioproduction. In shaking flask subcultures, the strain maintained β-carotene production for over ~30 generations. However, in continuous fermentations, subpopulation shifted toward faster-growing low-producers, leading to significant production losses within just ~18 growth generations. This process was accelerated by O2 limitation and high bioreactor dilution rates. Using canola oil as a carbon source increases population heterogeneity but enhances β-carotene biosynthesis and prolongs production compared with glucose-based media. Kinetic modeling suggests that strains optimized for the highest production in laboratory settings may be less robust in industrial environments, where suboptimal yet faster-growing variants gain a competitive edge under prolonged stress and ultimately shape overall continuous fermentation performance.
Date Issued
2026-01-01
Date Acceptance
2025-08-28
Citation
Trends in Biotechnology, 2026, 44 (1), pp.154-169
ISSN
0167-7799
Publisher
Elsevier BV
Start Page
154
End Page
169
Journal / Book Title
Trends in Biotechnology
Volume
44
Issue
1
Copyright Statement
© 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40987704
PII: S0167-7799(25)00356-7
Subjects
carotene
cell heterogeneity
kinetic model
oil feedstock
scale-up
strain stability
Yarrowia
Fermentation
beta Carotene
Bioreactors
Culture Media
Rapeseed Oil
Oxygen
Fatty Acids, Monounsaturated
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-09-22