Boosting succinic acid production of Yarrowia lipolytica at low pH through enhancing product tolerance and glucose metabolism.
Yarrowia lipolytica
Adaptive laboratory evolution
Glycolysis
Multi-omics analysis
Succinic acid
Journal
Microbial cell factories
ISSN: 1475-2859
Titre abrégé: Microb Cell Fact
Pays: England
ID NLM: 101139812
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
13
07
2024
accepted:
11
10
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
24
10
2024
Statut:
epublish
Résumé
Succinic acid (SA) is an important bio-based C4 platform chemical with versatile applications, including the production of 1,4-butanediol, tetrahydrofuran, and γ-butyrolactone. The non-conventional yeast Yarrowia lipolytica has garnered substantial interest as a robust cell factory for SA production at low pH. However, the high concentrations of SA, especially under acidic conditions, can impose significant stress on microbial cells, leading to reduced glucose metabolism viability and compromised production performance. Therefore, it is important to develop Y. lipolytica strains with enhanced SA tolerance for industrial-scale SA production. An SA-tolerant Y. lipolytica strain E501 with improved SA production was obtained through adaptive laboratory evolution (ALE). In a 5-L bioreactor, the evolved strain E501 produced 89.62 g/L SA, representing a 7.2% increase over the starting strain Hi-SA2. Genome resequencing and transcriptome analysis identified a mutation in the 26S proteasome regulatory subunit Rpn1, as well as genes involved in transmembrane transport, which may be associated with enhanced SA tolerance. By further fine-tuning the glycolytic pathway flux, the highest SA titer of 112.54 g/L to date at low pH was achieved, with a yield of 0.67 g/g glucose and a productivity of 2.08 g/L/h. This study provided a robust engineered Y. lipolytica strain capable of efficiently producing SA at low pH, thereby reducing the cost of industrial SA fermentation.
Sections du résumé
BACKGROUND
BACKGROUND
Succinic acid (SA) is an important bio-based C4 platform chemical with versatile applications, including the production of 1,4-butanediol, tetrahydrofuran, and γ-butyrolactone. The non-conventional yeast Yarrowia lipolytica has garnered substantial interest as a robust cell factory for SA production at low pH. However, the high concentrations of SA, especially under acidic conditions, can impose significant stress on microbial cells, leading to reduced glucose metabolism viability and compromised production performance. Therefore, it is important to develop Y. lipolytica strains with enhanced SA tolerance for industrial-scale SA production.
RESULTS
RESULTS
An SA-tolerant Y. lipolytica strain E501 with improved SA production was obtained through adaptive laboratory evolution (ALE). In a 5-L bioreactor, the evolved strain E501 produced 89.62 g/L SA, representing a 7.2% increase over the starting strain Hi-SA2. Genome resequencing and transcriptome analysis identified a mutation in the 26S proteasome regulatory subunit Rpn1, as well as genes involved in transmembrane transport, which may be associated with enhanced SA tolerance. By further fine-tuning the glycolytic pathway flux, the highest SA titer of 112.54 g/L to date at low pH was achieved, with a yield of 0.67 g/g glucose and a productivity of 2.08 g/L/h.
CONCLUSION
CONCLUSIONS
This study provided a robust engineered Y. lipolytica strain capable of efficiently producing SA at low pH, thereby reducing the cost of industrial SA fermentation.
Identifiants
pubmed: 39443950
doi: 10.1186/s12934-024-02565-0
pii: 10.1186/s12934-024-02565-0
doi:
Substances chimiques
Glucose
IY9XDZ35W2
Succinic Acid
AB6MNQ6J6L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
291Subventions
Organisme : National Natural Science Foundation of Shandong Province
ID : ZR2022ZD24
Organisme : National Natural Science Foundation of China
ID : 22208192
Organisme : Major Scientific and Technological Innovation Project of Shandong Province
ID : 2022CXGC020712-4
Informations de copyright
© 2024. The Author(s).
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