The Discovery of New Cyanobactins from Cyanothece PCC 7425 Defines a New Signature for Processing of Patellamides

• Published in: Chembiochem : a European journal of chemical biology Vol. 13; no. 18; pp. 2683 - 2689
• Main Authors: Houssen, Wael E., Koehnke, Jesko, Zollman, David, Vendome, Jeremie, Raab, Andrea, Smith, Margaret C. M., Naismith, James H., Jaspars, Marcel
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21.12.2012; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Amino Acid Sequence; Biochemistry & Molecular Biology; biosynthetic engineering; Chemistry, Medicinal; Crystal structure; cyanobactins; Cyanothece - metabolism; Life Sciences & Biomedicine; Models, Molecular; Molecular Sequence Data; natural products; Peptides, Cyclic - chemistry; Peptides, Cyclic - metabolism; Pharmacology & Pharmacy; Protein Processing, Post-Translational; Protein Structure, Tertiary; ribosomal peptides; Science & Technology; Serine Proteases - chemistry; Serine Proteases - metabolism; subtilisin proteases; subtilisin proteases; SUBTILISIN; ribosomal peptides; cyanobactins; biosynthetic engineering; PEPTIDE; MARINE NATURAL-PRODUCTS; REFINEMENT; natural products; GENE-CLUSTER; BIOSYNTHESIS; SEQUENCE; EXPRESSION; MACROCYCLIZATION; LISSOCLINUM-PATELLA
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201200661

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. Follow the signal: The discovery of new cyanobactins from Cyanothece PCC 7425 cultured under stressful conditions revealed a novel signature signal for its subtilisin protease that is homologous to the patellamide protease PatA. The crystal structure of the latter and modelling studies have provided a molecular rationalisation for the enzyme specificity, a step which will enhance harnessing the full capacity of these biosynthetic enzymes.