Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coli

Helena Shomar, Sophie Gontier, Niels J.F. van Den Broek, Héctor Tejeda Mora, Marek J. Noga, Peter Leon Hagedoorn, Gregory Bokinsky*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)


Carbapenems, a family of β-lactam antibiotics, are among the most powerful bactericidal compounds in clinical use. However, as rational engineering of native carbapenem-producing microbes is not currently possible, the present carbapenem supply relies upon total chemical synthesis of artificial carbapenem derivatives. To enable access to the full diversity of natural carbapenems, we have engineered production of a simple carbapenem antibiotic within Escherichia coli. By increasing concentrations of precursor metabolites and identifying a reducing cofactor of a bottleneck enzyme, we improved productivity by 60-fold over the minimal pathway and surpassed reported titers obtained from carbapenem-producing Streptomyces species. We stabilized E. coli metabolism against antibacterial effects of the carbapenem product by artificially inhibiting membrane synthesis, which further increased antibiotic productivity. As all known naturally occurring carbapenems are derived from a common intermediate, our engineered strain provides a platform for biosynthesis of tailored carbapenem derivatives in a genetically tractable and fast-growing species.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalNature Chemical Biology
Publication statusPublished - 25 Jun 2018


Dive into the research topics of 'Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coli'. Together they form a unique fingerprint.

Cite this