Mikrobiyhteisöjen laajentaminen tuotantomittakaavaan

Microbial fermentations are used to produce pharmaceuticals, chemicals, and fuels. Side product formation along with considerable losses in productivities and yields are often encountered in transition from laboratory- to production-scale. This is mainly caused by inevitable heterogeneity of large, stirred reactors with aeration, especially in the commonly used fed-batch operation mode. Previous studies of this challenge have proposed either improving reactor homogeneity or increasing tolerance of the production host. Microbial co-cultures have also been suggested because they facilitate side-product utilization. Purpose of this work was to examine the scale-up of microbial co-cultures. More specifically it was studied whether the adverse conditions caused by scale-up affect co-cultures less than the respective monocultures. In this work monocultures of two bacterial species, Escherichia coli and Acinetobacter baylyi, and four co-cultures of them with and without gene deletions were cultivated in batch-mode in a 1 L aerated stirred reactor. Both batch and fed-batch operation modes were simulated with a model that incorporated a 70-compartment hydrodynamic representation of a 30 m3 reactor, population balances, and unstructured kinetics. The simulations were performed also with an ideal reactor model at the 1 L-scale. Due to internal recycling of acetate, which inhibited E. coli but was the preferred substrate for A. baylyi, the co-cultures had 10 % to 50 % higher specific growth rates compared to the single strain cultivations. Simulations showed more modest improvements ranging from 3 % to 20 % in both studied scales. Specific growth rates and consequently biomass productivities were consistently smaller at the simulated large-scale with both mono- and co-cultures. Based on the simulations it seems that co-cultures do not scale-up any better than the respective monocultures, but appropriate scale-down experiments are required for verification. However, they do have the potential to alleviate side-product inhibition also at industrial scale