Identification and Characterization of the Echinocandin B Biosynthetic Gene Cluster from Emericella rugulosa NRRL 11440

摘要: Echinocandins are a family of fungal lipidated cyclic hexapeptide natural products. Due to their effectiveness as antifungal agents, three semisynthetic derivatives have been developed and approved for treatment human invasive candidiasis. All six the amino acid residues hydroxylated, including 4R,5R-dihydroxy-l-ornithine, 4R-hydroxyl-l-proline, 3S,4S-dihydroxy-l-homotyrosine, 3S-hydroxyl-4S-methyl-l-proline. We report here biosynthetic gene cluster echinocandin B 1 from Emericella rugulosa NRRL 11440 containing genes encoding six-module nonribosomal peptide synthetase EcdA, an acyl-AMP ligase EcdI, oxygenases EcdG, EcdH, EcdK. showed EcdI activates linoleate linoleyl-AMP installs it on first thiolation domain EcdA. also established through ATP–PPi exchange assay that EcdA loads l-ornithine in module. A separate hty encodes four enzymes de novo generation l-homotyrosine acetyl-CoA 4-hydroxyphenyl-pyruvate is...