Department of Biological Sciences (BIO)

Guest lecture by Prof. Brett A. Neilan - Engineering cyanobacteria and their toxin biosynthesis pathways for unnatural production

Thursday, 24.09.2015 at 10:15 am at Department of Biology, A-blokken, Thormøhlensgt 53, Room: K1/K2

Picture of Cyanobacteria

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The past two decades has witnessed major advances in our understanding of natural product biosynthesis, including the genetic basis for toxin production by a number of groups of bacteria and fungi. Cyanobacteria produce an unparalleled array of bioactive secondary metabolites, including alkaloids, polyketides and non-ribosomal peptides, some of which are potent toxins. Most cyanobacterial genera have either been shown to produce non-ribosomal peptides or have them encoded within their genomes. Early work on the genetics of cyanobacterial toxicity led to the discovery of one of the first examples of hybrid peptide-polyketide synthetases. This enzyme complex directed the production of the cyclic heptapeptide, microcystin, while a homologous gene cluster responsible for the synthesis of the pentapeptide nodularin, provided evidence of genetic recombination and possible gene transfer. More recently, hybrid peptide and polyketide synthetic pathways have been implicated in the production of the alkaloid cylindrospermopsin, and this information, in-turn, has provided the first evidence of genes involved in bacterial non-terpene alkaloid biosynthesis. Candidate gene loci involved in saxitoxin production have been identified in diverse cyanobacteria and algae. Genomic information has also indicated the cellular regulators of toxin production, as well as associated transport mechanisms. Exploiting what we refer to as toxins, such as microcystin, is the beginning of the unlimited potential in natural product biosynthetic engineering for the creation of unnatural antibiotics, antivirals, and immunosuppressants. Current directions in drug design and sustainable production, bioprospecting, and ethnopharmacology will be discussed as outcomes of this work.   



About Brett Neilan

Brett Neilan is a molecular biologist and an expert in the study of toxic cyanobacteria. Today his research group at the University of New South Wales (UNSW), comprises more than thirty researchers, including twenty graduate students. The main topic of their work is the genetics of toxic cyanobacteria (blue-green algae) and the research has led to an understanding of the biochemical pathways that are responsible for the production of toxins in our water supplies. He obtained his PhD in microbial and molecular biology from UNSW in 1995. Prior to his PhD training, Brett obtained a bachelor of applied science degree in biomedical science (1985) at the University of Technology, Sydney and then worked as a medical researcher, hospital scientist and forensic biologist. His postdoctoral position as an Alexander von Humboldt Fellowship in Berlin was on non-ribosomal peptide biosynthesis genetics. The continuation of this early work and a NASA internship at Stanford University has become the basis for current studies regarding the search for microbial natural products in novel environments, including Antarctica, the hypersaline lagoon of Shark Bay, WA, and Indonesian volcanoes. The research has been communicated in more than 180 peer-reviewed publications and was awarded the Australian Museum Eureka Prizes for Scientific Research in 2001, Interdisciplinary Science in 2005, and Environmental Science in 2009, and the Australian Academy of Science Fenner Medal for studies in the Biological Sciences. He is an adjunct professor at the Chinese Academy of Sciences and has recently been a visiting scientist in Italy, Japan, Brazil, Thailand, and Korea. Future plans are to characterise the genetics of marine toxins and gain a better understanding of the factors that influence the production of microbial toxins. Brett will also be looking at the mechanisms responsible for the complex biosynthesis of a range of pharmacologically active compounds to assist in the design and synthesis of novel bioactive products in a photosynthetic bioreactor.