ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
14 Oct 2024
14 Oct 2024
Historique:
received:
23
01
2024
accepted:
20
09
2024
medline:
15
10
2024
pubmed:
15
10
2024
entrez:
14
10
2024
Statut:
aheadofprint
Résumé
Repurposing an organelle for specialized metabolism provides an avenue for fermentable, unicellular organisms such as Saccharomyces cerevisiae to mimic compartmentalization of metabolic pathways within different plant tissues. Peroxisomes are attractive organelles for repurposing as they are not required for yeast viability when grown on glucose and can efficiently compartmentalize heterologous enzymes to enable physical separation of cytosolic native metabolism and peroxisomal engineered metabolism. However, when not required, peroxisomes are repressed, leading to low functional capacities for heterologous proteins. Here we engineer peroxisomes with enhanced functional capacities, with the goal of compartmentalizing up to eight metabolic enzymes to enhance titers. We implement a machine learning pipeline that allows the identification of factors to overexpress, culminating in a 137% increase in peroxisome functional capacity compared to a wild-type strain. Improved pathway compartmentalization enables an 80% increase in the biosynthesis titers of the monoterpene geraniol, up to 9.5 g L
Identifiants
pubmed: 39402374
doi: 10.1038/s41589-024-01759-2
pii: 10.1038/s41589-024-01759-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Organisme : National Science Foundation (NSF)
ID : DBI-1548297
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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