Lightning Oral Talk 25th Annual Lorne Proteomics Symposium 2020

Understanding glycopeptide antibiotic synthesis by mass spectrometric analysis of polycyclic peptides (#22)

Robert JA Goode 1 2 , Milda Kaniusaite 2 3 , Edward A Marschall 2 3 , Yongwei Zhao 2 3 , Anja Greule 2 3 , Julien Tailhades 2 3 , Max J Cryle 2 3 , Ralf B Schittenhelm 1 2
  1. Monash Proteomics and Metabolomics Facility, Monash University, Clayton, Victoria, Australia
  2. Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  3. EMBL Australia, Monash University, Clayton, Victoria, Australia

Glycopeptide antibiotics are considered the last line of defence against several bacterial infections. A thorough understanding of their biosynthesis and the ability to interrogate and manipulate their structure is therefore critical to overcome antibiotic resistance and to further develop efficient antibiotics.  Glycopeptide antibiotics typically consist of a core of seven non-standard amino acids generated through non-ribosomal peptide synthesis with up to four side chain crosslinks that are introduced by cytochrome P450 enzymes.  Mass spectrometric analysis of these samples is challenging due to the lack of available software to handle the non-standard amino acids as well as the complex crosslinking.  Here we present the results of different core peptides and enzyme combinations to understand the roles and specificities of these enzymes in the crosslinking process, and also highlight some of the challenges involved in analysing MSMS spectra from these samples.