Complete Genome Assembly of Amycolatopsis bartoniae DSM 45807T Allows the Characterization of a Novel Glycopeptide Biosynthetic Gene Cluster

Background: Glycopeptide antibiotics (GPAs) are a very successful class of clinically relevant antibacterials, used to treat severe infections caused by Gram-positive pathogens, e.g., multidrug resistant and methicillin-resistant staphylococci. The biosynthesis of GPAs is coded within large biosynthetic gene clusters (BGCs). In recent years, modern DNA sequencing technologies have allowed the identification and characterization of multiple novel GPA BGCs, leading to the discovery of novel compounds. Our previous research anticipated that the genome of Amycolatopsis bartoniae DSM 45807T carries a novel GPA BGC, although the genomic sequence quality available at that time did not allow us to characterize its organization properly. Objectives: To address this gap, in the current work we aimed to produce a complete genome assembly of A. bartoniae DSM 45807, and to identify and analyze the corresponding GPA BGC. Methods: Bioinformatic and microbiological methods were utilized in this research. Results: We de novo sequenced and completely assembled the genome of A. bartoniae DSM 45807, and fully characterized the BGC of interest, named aba. This BGC has an unusual gene organization and it contains four genes for sulfotransferases, which are considered to be rare in GPA BGCs. Our pathway prediction indicated that aba encodes the biosynthesis of a putatively novel GPA, although we were not able to detect any GPA production under different cultivation conditions, implying that aba pathway is inactive. Conclusions: Our results indicate aba as a promising source for new GPA tailoring enzymes.