Invited Speaker 11th Asia-Pacific Congress of the International Society on Toxinology 2021

Biosynthesis of cyanobacterial toxins in a heterologous host (#56)

Brett A Neilan 1
  1. University of Newcastle, Callaghan, NSW, Australia

Marine and freshwater cyanobacteria produce a variety of toxic compounds that pose a threat to the health of humans, livestock and natural ecosystems world-wide. Significant research efforts have been directed towards understanding the biosynthesis of these cyanotoxins in an attempt to reduce their deleterious effects on water quality and, more recently, to harness their biotechnological potential. A variety of complementary methods,  such as bioinformatic analyses and isotope feeding studies, have been employed over the last three decades to address knowledge gaps in this field. While many biosynthetic gene clusters that encode cyanobacterial natural products are known, the slow growth and a lack of genetic tools in the native producers hampers their modification, characterisation and large-scale production. By engineering heterologous hosts for the expression of cyanobacterial toxin biosythesis genes, sufficient material can be produced for research or industry. Although several hosts have been evaluated for the expression of cyanobacterial natural products, this presentation will detail the process of expressing toxin gene clusters in Escherichia coli using promoter exchanges. This talk focus on the utility of heterologous expression and biochemical studies, including emerging technologies for engineering and expressing complete cyanotoxin gene clusters.

  1. Liu T, Mazmouz R, Ongley SE, Chau R, Pickford R, Woodhouse JN, Neilan BA (2017) Directing the heterologous production of specific cyanobacterial toxin variants. ACS Chem Biol 12(8):2021-9.
  2. Ongley SE, Bian X, Zhang Y, Chau R, Gerwick WH, Müller R, Neilan BA (2013) High titer heterologous production of Lyngbyatoxin in E. coli, a protein kinase C activator from an uncultured marine Cyanobacterium. ACS Chem Biol 8 (9):1888-93.
  3. Cullen A, Pearson LA, Mazmouz R, Liu T, Soeriyadi AH, Ongley SE, Neilan BA (2019) Heterologous expression and biochemical characterisation of cyanotoxin biosynthesis pathways. Nat Prod Rep 36(8):1117-1136.