@misc{NeilanPearsonMuenchhoffetal.2013, author = {Neilan, Brett A. and Pearson, Leanne A. and M{\"u}nchhoff, Julia and Moffitt, Michelle C. and Dittmann-Th{\"u}nemann, Elke}, title = {Environmental conditions that influence toxin biosynthesis in cyanobacteria}, series = {Environmental microbiology}, volume = {15}, journal = {Environmental microbiology}, number = {5}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1462-2912}, doi = {10.1111/j.1462-2920.2012.02729.x}, pages = {1239 -- 1253}, year = {2013}, abstract = {Over the past 15 years, the genetic basis for production of many cyanobacterial bioactive compounds has been described. This knowledge has enabled investigations into the environmental factors that regulate the production of these toxins at the molecular level. Such molecular or systems level studies are also likely to reveal the physiological role of the toxin and contribute to effective water resource management. This review focuses on the environmental regulation of some of the most relevant cyanotoxins, namely the microcystins, nodularin, cylindrospermopsin, saxitoxins, anatoxins and jamaicamides.}, language = {en} } @misc{DittmannThuenemannFewerNeilan2013, author = {Dittmann-Th{\"u}nemann, Elke and Fewer, David P. and Neilan, Brett A.}, title = {Cyanobacterial toxins biosynthetic routes and evolutionary roots}, series = {FEMS microbiology reviews}, volume = {37}, journal = {FEMS microbiology reviews}, number = {1}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0168-6445}, doi = {10.1111/j.1574-6976.2012.12000.x}, pages = {23 -- 43}, year = {2013}, abstract = {Cyanobacteria produce an unparalleled variety of toxins that can cause severe health problems or even death in humans, and wild or domestic animals. In the last decade, biosynthetic pathways have been assigned to the majority of the known toxin families. This review summarizes current knowledge about the enzymatic basis for the production of the hepatotoxins microcystin and nodularin, the cytotoxin cylindrospermopsin, the neurotoxins anatoxin and saxitoxin, and the dermatotoxin lyngbyatoxin. Elucidation of the biosynthetic pathways of the toxins has paved the way for the development of molecular techniques for the detection and quantification of the producing cyanobacteria in different environments. Phylogenetic analyses of related clusters from a large number of strains has also allowed for the reconstruction of the evolutionary scenarios that have led to the emergence, diversification, and loss of such gene clusters in different strains and genera of cyanobacteria. Advances in the understanding of toxin biosynthesis and evolution have provided new methods for drinking-water quality control and may inspire the development of techniques for the management of bloom formation in the future.}, language = {en} } @misc{PearsonDittmannMazmouzetal.2016, author = {Pearson, Leanne A. and Dittmann, Elke and Mazmouz, Rabia and Ongley, Sarah E. and Neilan, Brett A.}, title = {The genetics, biosynthesis and regulation of toxic specialized metabolites of cyanobacteria}, series = {Harmful algae}, volume = {54}, journal = {Harmful algae}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1568-9883}, doi = {10.1016/j.hal.2015.11.002}, pages = {98 -- 111}, year = {2016}, abstract = {The production of toxic metabolites by cyanobacterial blooms represents a significant threat to the health of humans and ecosystems worldwide. Here we summarize the current state of the knowledge regarding the genetics, biosynthesis and regulation of well-characterized cyanotoxins, including the microcystins, nodularin, cylindrospermopsin, saxitoxins and antitoxins, as well as the lesser-known marine toxins (e.g. lyngbyatoxin, aplysiatoxin, jamaicamides, barbamide, curacin, hectochlorin and apratoxins). (C) 2015 Elsevier B.V. All rights reserved.}, language = {en} } @misc{WoodhouseMakowerYeungetal.2016, author = {Woodhouse, Jason Nicholas and Makower, A. Katharina and Yeung, Anna C. Y. and Ongley, Sarah E. and Micallef, Melinda L. and Moffitt, Michelle C. and Neilan, Brett A.}, title = {Advances in genomics, transcriptomics and proteomics of toxin-producing cyanobacteria}, series = {Environmental microbiology reports}, volume = {8}, journal = {Environmental microbiology reports}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1758-2229}, doi = {10.1111/1758-2229.12366}, pages = {3 -- 13}, year = {2016}, abstract = {A common misconception persists that the genomes of toxic and non-toxic cyanobacterial strains are largely conserved with the exception of the presence or absence of the genes responsible for toxin production. Implementation of -omics era technologies has challenged this paradigm, with comparative analyses providing increased insight into the differences between strains of the same species. The implementation of genomic, transcriptomic and proteomic approaches has revealed distinct profiles between toxin-producing and non-toxic strains. Further, metagenomics and metaproteomics highlight the genomic potential and functional state of toxic bloom events over time. In this review, we highlight how these technologies have shaped our understanding of the complex relationship between these molecules, their producers and the environment at large within which they persist.}, language = {en} } @article{SoeriyadiOngleyKehretal.2021, author = {Soeriyadi, Angela H. and Ongley, Sarah E. and Kehr, Jan-Christoph and Pickford, Russel and Dittmann, Elke and Neilan, Brett A.}, title = {Tailoring enzyme stringency masks the multispecificity of a lyngbyatoxin (indolactam alkaloid) nonribosomal peptide synthetase}, series = {ChemBioChem}, volume = {23}, journal = {ChemBioChem}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1439-4227}, doi = {10.1002/cbic.202100574}, pages = {6}, year = {2021}, abstract = {Indolactam alkaloids are activators of protein kinase C (PKC) and are of pharmacological interest for the treatment of pathologies involving PKC dysregulation. The marine cyanobacterial nonribosomal peptide synthetase (NRPS) pathway for lyngbyatoxin biosynthesis, which we previously expressed in E. coli, was studied for its amenability towards the biosynthesis of indolactam variants. Modification of culture conditions for our E. coli heterologous expression host and analysis of pathway products suggested the native lyngbyatoxin pathway NRPS does possess a degree of relaxed specificity. Site-directed mutagenesis of two positions within the adenylation domain (A-domain) substrate-binding pocket was performed, resulting in an alteration of substrate preference between valine, isoleucine, and leucine. We observed relative congruence of in vitro substrate activation by the LtxA NRPS to in vivo product formation. While there was a preference for isoleucine over leucine, the substitution of alternative tailoring domains may unveil the true in vivo effects of the mutations introduced herein.}, language = {en} }