TY  - JOUR
A1  - Pancrace, Claire
A1  - Ishida, Keishi
A1  - Briand, Enora
A1  - Pichi, Douglas Gatte
A1  - Weiz, Annika R.
A1  - Guljarmow, Arthur
A1  - Scalvenzi, Thibault
A1  - Sassoon, Nathalie
A1  - Hertweck, Christian
A1  - Dittmann, Elke
A1  - Gugger, Muriel
T1  - Unique Biosynthetic Pathway in Bloom-Forming Cyanobacterial Genus Microcystis Jointly Assembles Cytotoxic Aeruginoguanidines and Microguanidines
JF  - ACS chemical biology
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.1021/acschembio.8b00918
SN  - 1554-8929
SN  - 1554-8937
VL  - 14
IS  - 1
SP  - 67
EP  - 75
PB  - American Chemical Society
CY  - Washington
ER  -