Heterologous Expression of Epoxomicin in Escherichia coli.
ACS Synth Biol
; 13(9): 2702-2709, 2024 Sep 20.
Article
in En
| MEDLINE
| ID: mdl-39116310
ABSTRACT
Epoxomicin is an epoxyketone proteasome inhibitor with synthetic derivatives approved or under investigation for treatment of multiple myeloma. To leverage the advantages of Escherichia coli as a rapidly growing and readily engineered host for the production of epoxomicin and analogues, we expressed codon-optimized versions of the epoxomicin biosynthetic genes, epxD, epxE, and epxF. Epoxomicin was detected, but the major product was a ketone resulting from α,ß-keto acid precursor decarboxylation. Epoxomicin yield was improved by altering the copy numbers of each gene and creating a fusion of epxE and epxF. Our optimized system offers promise for efficient engineering and biosynthesis of improved epoxomicin analogues.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Escherichia coli
Language:
En
Journal:
ACS Synth Biol
/
ACS synth. biol
/
ACS synthetic biology
Year:
2024
Document type:
Article
Affiliation country:
Nueva Zelanda
Country of publication:
Estados Unidos