One pathway, two cyclic non-ribosomal pentapeptides: Heterologous expression of BE-18257 antibiotics and pentaminomycins from streptomyces cacaoi CA-170360

Abstract

The strain Streptomyces cacaoi CA-170360 produces the cyclic pentapeptides pentamino-mycins A–H and BE-18257 A–C, two families of cyclopeptides synthesized by two non-ribosomal peptide synthetases encoded in tandem within the same biosynthetic gene cluster. In this work, we have cloned and confirmed the heterologous expression of this biosynthetic gene cluster, demon-strating that each of the non-ribosomal peptide synthetases present in the cluster is involved in the biosynthesis of each group of cyclopeptides. In addition, we discuss the involvement of a stand-alone enzyme belonging to the Penicillin Binding Protein family in the release and macrocyclization of the peptides.