Modelling of the Dynamics of Aminoacid Pools; its relevance to commercial yeast propagations
Presented at: European Research Conference:
'Control of Metabolic Flux; Approaches to understanding the control of flux in yeasts and fungi'
14-18 June 1997 Giens, France
Summary:
The amount of data and fragmented knowledge on yeast metabolism is growing enormously in the past years. Unfortunately, until now this potential has not be fully exploited to optimize or redesign commercial yeast processes ranging from yeast extract manufacture to enzyme production.
To a large extend this is due to the reductionistic approach in research. The isolated enzyme or pathway is studied in detail in a well defined environment. The translation into commercial strains, media and process conditions is still a bottle neck and far from optimal. An alternative approach is the holistic (systems) approach to describe the microbial metabolism. However, this is still underdeveloped.
Examples of commercial propagations and related metabolic phenomena will be given. These phenomena are studied using alternative tools such as accelero stats and continuous phased cultures.
The model approach will be outlined in comparison with MCA, Flux Analysis and structured cybernetic modelling (e.g. Savinell 1992, Bellgardt, 1988). The goal of the models is to describe / predict semi-quantitatively the metabolic behaviour of a growing microorganism. There is a strong need to have these tools to guide (industrial) research on micro-organisms and higher organisms.
Central nitrogen metabolism around glutamate/ glutamine has been studied at the level of translational regulation, enzyme activity and metabolite levels (ter Schure 1996). After network identification and Flux Analysis based on steady state fluxes and defined pulses of glutamine and ammonium, parameters were estimated. This model has been validated successfully with data obtained from a glutamine synthase negative strain.
The potential of cybernetic modelling will be illustrated to some extend. This type of modelling shows is a strong analogy with modelling a factory operation.
References:
- Bellgardt, K.-H., A new approach for structured growth models, In: 4th Int Conf. Computer Appl. in Fermentation Technology, Eds. N.M. Fish, R.I. Fox, Cambridge, 1988. pg 79-92
- Savinell, J.M., Palsson, B.O., J. Theor. Biol. 154(1992) 421-454.
- ter Schure, E. G., PhD Thesis, Rijks Universiteit Utrecht, 1996.