Final Activity Report Summary - TERPENOID REGULATION (Role of creA on the regulation of terpenoid biosynthesis in Fusarium) Fusarium fujikuroi produces many secondary metabolites with biotechnological applications, such as carotenoids and gibberellins (GAs), and terpenoid products sharing the first biosynthetic steps. This fungus is the industrial source for GAs, which are plant hormones with many applications in agriculture. We studied the carbon regulation of the carotenoid and GA biosynthetic pathways. We found some unexpected but interesting results for the production of bikaverin, an antibiotic polyketide synthesized under GA producing conditions. The carbon source had a minor influence on the amounts of carotenoids produced by f. fujikuroi, however large differences in the composition of the carotenoid mixture were appreciated with different carbohydrates. Bikaverin and GAs were only produced in the absence of nitrogen. Under appropriate producing conditions, minor variations of GA production were found in different carbon sources, indicating a minor role of catabolite repression for this pathway. Similar results were found for bikaverin, apart from sucrose, which led to a dramatic increase in bikaverin accumulation. This sucrose-mediated stimulation, effective only in the absence of glucose, was not achieved at the transcription level, as shown by the lack of induction under these conditions of the pksA gene, coding for the key enzyme of bikaverin biosynthesis. The results confirmed regulatory differences between these biosynthetic pathways and opened a way for the independent control of bikaverin production in the GA fermentation industry. Experiments that were in progress by the time of the project completion were anticipated to help us to understand the role of the CreA protein in the regulation of these secondary metabolites in f. fujikuroi.
