Biosynthesis and Heterologous Production of Argyrins

Domen Pogorevc, Ying Tang, Michael Hoffmann, Gregor Zipf, Hubert S Bernauer, Alexander Popoff, Heinrich Steinmetz, Silke C Wenzel

Research output: Contribution to journalOriginal Article (Journal)peer-review

Abstract

Argyrins represent a family of cyclic octapeptides exhibiting promising antimicrobial, antitumorigenic and immunosuppressant activities. They derive from a nonribosomal peptide synthetase pathway, which was identified and characterized in this study from the myxobacterial producer strain Cystobacter sp. SBCb004. Using the native biosynthetic gene cluster (BGC) sequence as template synthetic BGC versions were designed and assembled from gene synthesis fragments. A heterologous expression system was established after chromosomal deletion of a well-expressed lipopeptide pathway from the host strain Myxococcus xanthus DK1622. Different approaches were applied to engineer and improve heterologous argyrin production, which was finally increased to 160 mg/L, around 20-fold higher yields compared to the native producer. Heterologous production platform also led to identification of several novel argyrin derivatives (A2, F3, G3, I, J, K, and L). The optimized production system provides a versatile platform for future supply of argyrins and novel derivatives thereof.

Original languageEnglish
Pages (from-to)1121-1133
Number of pages13
JournalACS synthetic biology.
Volume8
Issue number5
DOIs
Publication statusPublished - 17 May 2019
Externally publishedYes

Keywords

  • Bacterial Proteins/genetics
  • Metabolic Engineering/methods
  • Multigene Family
  • Myxococcus xanthus/metabolism
  • Peptide Synthases/genetics
  • Peptides, Cyclic/biosynthesis

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