Limiting reactions in activation of acyl units in biosynthesis of macrolide antibiotics.

A Single Sfp-Type Phosphopantetheinyl Transferase Plays a Major Role in the Biosynthesis of PKS and NRPS Derived Metabolites in Streptomyces ambofaciens ATCC23877

The phosphopantetheinyl transferases (PPTases) are responsible for the activation of the carrier protein domains of the polyketide synthases (PKS), non ribosomal peptide synthases (NRPS) and fatty acid synthases (FAS). The analysis of the Streptomyces ambofaciens ATCC23877 genome has revealed the presence of four putative PPTase encoding genes. One of these genes appears to be essential and is ...

Bioassay-Guided Evolution of Glycosylated Macrolide Antibiotics in Escherichia coli

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 tran...

A Sorangium cellulosum (myxobacterium) gene cluster for the biosynthesis of the macrolide antibiotic soraphen A: cloning, characterization, and homology to polyketide synthase genes from actinomycetes.

A 40-kb region of DNA from Sorangium cellulosum So ce26, which contains polyketide synthase (PKS) genes for synthesis of the antifungal macrolide antibiotic soraphen A, was cloned. These genes were detected by homology to Streptomyces violaceoruber genes encoding components of granaticin PKS, thus extending this powerful technique for the identification of bacterial PKS genes, which has so far ...

Structure activity relationship in sixteen membered macrolide antibiotics.

Leucomycin (Kitasamycin) is a macrolide antibiotic having activity against gram-positive bacteria and certain Mycoplasma strains. Comparison of antimicrobial activities of the variuos leucomycin congeners (I-X) indicates a clear structure-activity relationship among them. The acylation of the 3-hydroxy group somewhat reduces the in vitro activity while the acylation of the 4"-hydroxy group of m...

Hybrid biosynthesis and absolute configuration of macrolide antibiotic M-4365 G1.