How many microbiologists does it take to change a light bulb? None, as it turns out - the dozens of attendees at June's Joint Academic Microbiology Seminars (JAMS) at the Australian Museum waited patiently through a short blackout for drinks, snacks, and three servings of fresh scientific discussion.
Regulation and heterologous expression of bioactive natural products from the filamentous marine cyanobacterium Lyngbya majuscula.
The marine cyanobacterium Lyngbya majuscula is well recognized as a rich source of bioactive secondary metabolites that are valued as both drug candidates and resources in biotechnological applications. Although considerable advances have been made in understanding the gene clusters involved in molecule assemblies, the potential of many Lyngbya metabolites has yet to be harnessed because of low yields from field collections and slow growth in laboratory cultures. Two possible routes to improving Lyngbya natural product yields could be through discovery and manipulation of regulatory mechanisms associated with Lyngbya biosynthetic pathways, and establishment of a reliable heterologous expression platform for Lyngbya metabolites. In previous efforts studying the regulation of natural products from Lyngbya, we isolated light related transcription factor proteins that may be used to regulate production of the jamaicamides, neurotoxic compounds from a Jamaican Lyngbya strain. We have developed an approach to monitor rates of jamaicamide A and B biosynthesis in vivo using a combination of mass spectrometry and stable isotope feeding, and found different rates of biosynthesis between these two molecules in light and dark conditions. This approach has been used to measure the effects of a variety of culture conditions on natural product turnover in cyanobacteria. Current efforts towards heterologous pathway expression are focused on the dermatotoxic lyngbyatoxins from a Hawaiian Lyngbya collection. Functional Lyngbya recombinant protein expression has been achieved using the model actinomycete Streptomyces coelicolor, and we are now attempting to determine if Streptomyces is capable of expressing the entire lyngbyatoxin pathway.