Journal
FEBS JOURNAL
Volume 275, Issue 21, Pages 5343-5354Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1742-4658.2008.06664.x
Keywords
acidic lipopeptide antibiotics; AMP ligase; daptomycin; lipidation reaction; nonribosomal peptide synthetases
Categories
Funding
- Deutsche Forschungsgemeinschaft
- Fonds der Chemischen Industrie
Ask authors/readers for more resources
Daptomycin and A21987C antibiotics are branched, cyclic, nonribosomally assembled acidic lipodepsipeptides produced by Streptomyces roseosporus. The antibacterial activity of daptomycin against Gram-positive bacteria strongly depends on the nature of the N-terminal fatty acid moiety. Two genes, dptE and dptF, localized upstream of the daptomycin nonribosomal peptide synthetase genes, are thought to be involved in the lipidation of daptomycin. Here we describe the cloning, heterologous expression, purification and biochemical characterization of the enzymes encoded by these genes. DptE was proven to preferentially activate branched mid- to long-chain fatty acids under ATP consumption, and these fatty acids are subsequently transferred onto DptF, the cognate acyl carrier protein. Additionally, we demonstrate that lipidation of DptF by DptE in trans is based on specific protein-protein interactions, as DptF is favored over other acyl carrier proteins. Study of DptE and DptF may provide useful insights into the lipidation mechanism, and these enzymes may be used to generate novel daptomycin derivatives with altered fatty acids.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available