Unique Biosynthetic Pathway in Bloom-Forming Cyanobacterial Genus Microcystis Jointly Assembles Cytotoxic Aeruginoguanidines and Microguanidines

Type Article
Date 2019-01
Language English
Author(s) Pancrace Claire1, 2, Ishida Keishi3, Briand EnoraORCID4, Pichi Douglas Gatte5, Weiz Annika R.5, Guljarnow Arthur5, Scalvenzi Thibault1, Sassoon Nathalie1, Hertweck ChristianORCID3, 6, Dittmann ElkeORCID5, Gugger Muriel1
Affiliation(s) 1 : Inst Pasteur, Collect Cyanobacteries, 28 Rue Dr Roux, F-75724 Paris 15, France.
2 : UPMC, UPEC, CNRS 7618, IEES Paris,UMR 113,IRD 242,INRA 1392,PARIS 7 113, 4 Pl Jussieu, F-75005 Paris, France.
3 : Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Beutenbergstr 11a, D-07745 Jena, Germany.
4 : IFREMER, Lab Phycotoxines, Rue Ile Yeu, F-44311 Nantes, France.
5 : Univ Potsdam, Inst Biochem & Biol, Dept Microbiol, D-14476 Golm, Germany.
6 : Friedrich Schiller Univ Jena, Fac Biol Sci, D-07743 Jena, Germany.
Source Acs Chemical Biology (1554-8929) (Amer Chemical Soc), 2019-01 , Vol. 14 , N. 1 , P. 67-75
DOI 10.1021/acschembio.8b00918
WOS© Times Cited 18

The cyanobacterial genus Microcystis is known to produce an elaborate array of structurally unique and biologically active natural products, including hazardous cyanotoxins. Cytotoxic aeruginoguanidines represent a yet unexplored family of peptides featuring a trisubstituted benzene unit and farnesylated arginine derivatives. In this study, we aimed at assigning these compounds to a biosynthetic gene cluster by utilizing biosynthetic attributes deduced from public genomes of Microcystis and the sporadic distribution of the metabolite in axenic strains of the Pasteur Culture Collection of Cyanobacteria. By integrating genome mining with untargeted metabolomics using liquid chromatography with mass spectrometry, we linked aeruginoguanidine (AGD) to a nonribosomal peptide synthetase gene cluster and coassigned a significantly smaller product to this pathway, microguanidine (MGD), previously only reported from two Microcystis blooms. Further, a new intermediate class of compounds named microguanidine amides was uncovered, thereby further enlarging this compound family. The comparison of structurally divergent AGDs and MGDs reveals an outstanding versatility of this biosynthetic pathway and provides insights into the assembly of the two compound subfamilies. Strikingly, aeruginoguanidines and microguanidines were found to be as widespread as the hepatotoxic microcystins, but the occurrence of both toxin families appeared to be mutually exclusive.

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Pancrace Claire, Ishida Keishi, Briand Enora, Pichi Douglas Gatte, Weiz Annika R., Guljarnow Arthur, Scalvenzi Thibault, Sassoon Nathalie, Hertweck Christian, Dittmann Elke, Gugger Muriel (2019). Unique Biosynthetic Pathway in Bloom-Forming Cyanobacterial Genus Microcystis Jointly Assembles Cytotoxic Aeruginoguanidines and Microguanidines. Acs Chemical Biology, 14(1), 67-75. Publisher's official version : https://doi.org/10.1021/acschembio.8b00918 , Open Access version : https://archimer.ifremer.fr/doc/00481/59277/