Critical to the discovery process is the ability to produce sufficient amounts of active metabolites to complete the project. Many microbial discovery projects flounder at this point. When the amounts of an active produced by a microbe can be as low as 0.1 mg the prospect of producing grams of material can be daunting.
Fermentation lays the foundation for exploiting the chemical diversity found in microbes. Simply growing a microbe will not ensure production of metabolites. Unlocking the metabolic potential of a microbe requires the use of multiple fermentation conditions matched to its specific needs. A single media will only show part of the potential metabolite repertoire.
A screen shot of COMET in Compare mode demonstrates the co-metabolite patterns of MST MF283 extracts from three differing media (C, M and X). These patterns are analysed to ensure that media variations are delivering additional metabolic diversity.
Simply growing a microbe without optimising fermentation conditions will give you, at best, a 20% chance of successfully producing sufficient material for further work. By exploring an organism's metabolic dexterity under a range of fermentation conditions that 20% possibility can be converted to an 80% probability.
Microbial Screening optimisation strategies include a broad range of treatments that we have found influence metabolite production in particular types of microbes. These strategies are based on the results of studies undertaken with hundreds of cultures. Typically 10 to 100 fold improvements in production can be achieved.
The optimisation for MST-107825 (above) offers an insight into fermentation. The target NemaTOX activity was enhanced 32-fold by treatment 2M, while other treatments led to serendipitous increases in ProTOX and EuTOX activities.
Understanding production is the key to converting a novel active into a successful project.
Sometimes yield improvements simply cannot be achieved by changes in fermentation conditions. Microbial Screening's extensive culture library can provide a useful solution to production improvement problems. For example, a high producing strain for Oligomycin A, B, C and D was required for our research. The highest producing strain, while providing the target metabolites in mg quantities on solid medium, was not amenable to liquid fermentation. COMET analysis revealed that our culture library contains 40 Oligomycin producing strains! These could be classified into 5 distinct groups based on co-metabolite patterns. Cultures from two of these Oligomycin-producing groups were readily amenable to liquid fermentation. The strain diversity within Microbial Screening's culture library can overcome production difficulties.
Biodiversity is more than a source of novelty; it is also a tool for solving practical problems.