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  - 
TY  - JOUR
A1  - Krumbholz, Julia
A1  - Ishida, Keishi
A1  - Baunach, Martin
A1  - Teikari, Jonna
A1  - Rose, Magdalena M.
A1  - Sasso, Severin
A1  - Hertweck, Christian
A1  - Dittmann, Elke
T1  - Deciphering chemical mediators regulating specialized metabolism in a symbiotic cyanobacterium
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker. International edition
N2  - Genomes of cyanobacteria feature a variety of cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting the discovery and exploitation of the metabolic dark matter are not well understood. Here we describe the discovery of two cell density-dependent chemical mediators, nostoclide and nostovalerolactone, in the symbiotic model strain Nostoc punctiforme, and demonstrate their pronounced impact on the regulation of specialized metabolism. Through transcriptional, bioinformatic and labeling studies we assigned two adjacent biosynthetic gene clusters to the biosynthesis of the two polyketide mediators. Our findings provide insight into the orchestration of specialized metabolite production and give lessons for the genomic mining and high-titer production of cyanobacterial bioactive compounds.
KW  - Biosynthesis
KW  - Cyanobacteria
KW  - Genomic Mining
KW  - Quorum Sensing
KW  - Specialized
KW  - Metabolism
Y1  - 2022
U6  - https://doi.org/10.1002/anie.202204545
SN  - 1433-7851
SN  - 1521-3773
PB  - Wiley-VCH
CY  - Weinheim
ER  -