One Pathway, Two Cyclic Non-Ribosomal Pentapeptides: Heterologous Expression of BE-18257 Antibiotics and Pentaminomycins from <i>Streptomyces cacaoi</i> CA-170360

Abstract

The strain Streptomyces cacaoi CA-170360 produces the cyclic pentapeptides pentaminomycins 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, demonstrating 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.

Keywords

• pentaminomycin
• BE-18257
• heterologous expression
• Cas9-assisted targeting of chromosome segments (CATCH) cloning
• non-ribosomal peptide synthetases (NRPS)
• secondary metabolites