Engineering <i>Escherichia coli</i> for the Production of the PK/NRP Hybrid Antibiotic Salivabactin.

ABSTRACT: Salivabactin, a newly discovered hybrid polyketide/nonribosomal peptide (PK/NRP) antibiotic with a unique scaffold, exhibits potent activity against Gram-positive pathogens such as Streptococcus pyogenes. Despite its promising bioactivity, the low yield of the native producer Streptococcus salivarius (SAL) limits further investigation into salivabactin's mode of action and pharmaceutical applications. Here, we report the first heterologous production of salivabactin in Escherichia coli. The biosynthetic genes were co-expressed in E. coli, followed by optimizations in gene expression and precursor feeding to improve biosynthetic efficiency. Additional metabolic engineering strategies, including the knockout of a 4-hydroxybenzoic acid (4-HBA) exporter to increase

SUBMITTER: Ko YS 

PROVIDER: S-EPMC12360414 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature