Correlation Engine 2.0
Clear Search sequence regions


Macrolide antibiotics such as erythromycin are clinically important polyketide natural products. We have engineered a recombinant strain of Escherichia coli that produces small but measurable quantities of the bioactive macrolide 6-deoxyerythromycin D. Bioassay-guided evolution of this strain led to the identification of an antibiotic-overproducing mutation in the mycarose biosynthesis and transfer pathway that was detectable via a colony-based screening assay. This high-throughput assay was then used to evolve second-generation mutants capable of enhanced precursor-directed biosynthesis of macrolide antibiotics. The availability of a screen for macrolide biosynthesis in E. coli offers a fundamentally new approach in dissecting modular megasynthase mechanisms as well as engineering antibiotics with novel pharmacological properties.

Citation

Ho Young Lee, Chaitan Khosla. Bioassay-guided evolution of glycosylated macrolide antibiotics in Escherichia coli. PLoS biology. 2007 Feb;5(2):e45

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 17298179

View Full Text