OPPORTUNITIES FOR THE BIOPROCESS INTENSIFICATION OF THE BIOSYNTHESIS OF NATURAL PRODUCTS FROM CYANOBACTERIA

摘要

Lyngbya majuscula, is a tropical filamentous non-heterocystous nitrogen fixing marine cyanobacterium, responsible for toxic algal blooms, and produces over 150 novel and pharmaceutically active natural products. Recently, we discovered three new lipopeptides from a Tahitian (Moorea, French Polynesia) collection of L. majuscula. The isolation of these three compounds, from various locations and over subsequent years, seems to contradict previous results from L. majuscula. Indeed, it is commonly noted that this species shows great variability in natural product production both spatially and temporally. This variability, implies phenotypic influence and lends itself to bioprocess intensification for the production of targeted secondary metabolites by optimising fermentation yields via media composition, dynamic control of physical conditions, induction, genetics and novel bioreactor engineering. In order to characterise the mechanism of secondary metabolite production within this organism, natural product chemistry (HPLC, ~1H NMR and FTICR-MS), molecular biology and bioprocess engineering (reaction kinetics, process optimisation) techniques were employed. Specific investigations comprised: 1) physical factors effecting the production of these compounds and the mechanism of secondary metabolite production (at steady state, focussing on transport phenomenon and reaction kinetics). Structural genes have been sequenced and characterised in several cyanobacterial strains previously. However, this is the first time a non-heterocystous, filamentous, cyanobacterial species has been studied in detail, taking both specific phenotypic and genotypic factors into account. The environmental sample of L. majuscula was cultured within a 25 L bubble column photobioreactor (500 Lux, 20℃, 12hr light:dark cycle), sampled daily for a period of 3 months. Results obtained to date within this field of research will be presented.