The discovery of new cyanobactins from Cyanothece PCC 7425 defines a new signature for processing of patellamides

Wael E Houssen, Jesko Koehnke, David Zollman, Jeremie Vendome, Andrea Raab, Margaret C M Smith, James H Naismith, Marcel Jaspars

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Cyanobactins, including patellamides, are a group of cyanobacterial post-translationally modified ribosomal cyclic peptides. The final product should in theory be predictable from the sequence of the precursor peptide and the associated tailoring enzymes. Understanding the mechanism and recognition requirements of these enzymes will allow their rational engineering. We have identified three new cyanobactins from a Cyanothece PCC 7425 culture subjected to a heat shock. One of these compounds revealed a novel signature signal for ThcA, the subtilisin-like serine protease that is homologous to the patellamide protease PatA. The crystal structure of the latter and modelling studies allow rationalisation of the recognition determinants for both enzymes, consistent with the ribosomal biosynthetic origin of the new compounds.
Original languageEnglish
Pages (from-to)2683-2689
Number of pages7
JournalChemBioChem
Volume13
Issue number18
Early online date21 Nov 2012
DOIs
Publication statusPublished - 21 Dec 2012

Bibliographical note

Acknowledgements
This work was supported by the Leverhulme Trust Grant RPG-20120504 (M.J., M.C.M.S. and J.H.N.). M.C.M.S. acknowledges funding from the BBSRC project grant BB/F003439/1. We thank DNA sequencing & Services (MRCPPU, College of Life Sciences,University of Dundee, Scotland, (www.dnaseq.co.uk) for DNA sequencing. W.E.H. thanks Drs. Louise Thomas and Andrew McEwan (University of Aberdeen) for help with protein purification. W.E.H. is the recipient of a SULSA postdoctoral fellowship. J.K. thanks Judith Reeks (University of St Andrews) for helpful discussion and Drs Catherine Botting and Sally Shirran (University of St Andrews) for MS analysis of cPatApr and PatE cleavage. J.K.is the recipient of a DFG postdoctoral fellowship.

Keywords

  • biosynthetic engineering
  • cyanobactins
  • natural products
  • ribosomal peptides
  • subtilisin proteases

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