Using genetic algorithms coupling neural networks in a study of xylitol production: medium optimisation
Introduction
Xylitol is a polyol with some interesting properties which make it of high value to pharmaceutical, food and chemical industries etc. Despite this wide range of applications, the use of xyitol is limited by comparatively high production costs and this has encouraged the development of new technologies able to lower the production costs. The microbiological conversion of xylose solutions is a selective and promising process [1].
The bioconversion of pentose into polyalcohols is a complex process influenced by several factors. To improve xylitol fermentation, designing a fermentation medium is of critical importance because medium composition can significantly affect product concentration, yield, volumetric productivity, and the ease and cost of downstream product separation [2].
The optimisation of medium composition uses mainly the ‘one-at-a-time’ method and statistical approaches such as response surface methodology based on factorial design experiments [3], [4], [5], [6], [7], orthogonal array design based on statistical approaches [8] or uniform design based on numeral theory [9]. The ‘one-at-a-time’ method ignores interactions among the different medium components, optimal conditions may be missed and a large number of experiments are required. For the application of response surface methodology, a model must be assumed to determine the relative influence of the various medium components. This model is then used to calculate the optimal concentrations for the objective function. The common model used is a full second-order polynomial. The number of experiments is given by LN (N factors at L levels), therefore in practice only two or three levels can be applied and plotting is limited to two variables at a time. The level of orthogonal array design or uniform design is also limited by the factor.
Genetic algorithms (GAs) use evolutionary natural selection processes, where selection results in species that fit the best. GAs have proved to be extremely suitable for the optimisation of highly non-linear problems with many variables and for reported problems the global optimum was found [10]. Using GAs for medium optimisation, Freyer et al. [11] succeeded in increasing the biomass productivity. Deuster-Botz et al. [12], [13] optimised 12 concentrations of 12 medium components within 144 experiments to give maximum specific hydrocortisone dehydrogenase activity and biomass yield, and 14 medium components within 125 experiments to give a maximum formate-dehydrogenase activity with minimal use of nutrient salts. In the study of mevinolin biosynthesis by Aspergillus terreus, within four generations of fermentation experiments the productivity has increased nearly three times [14]. With GAs however no insight from the designer is used and historical data are abandoned on each iteration.
Neural networks (NNs) may provide considerable advantages in prediction against different biological backgrounds. Their strong points are that they work well with large amounts of data and require no mechanistic description of the system. This makes NNs particularly well suited to medium design [15].
In this paper, a new medium optimisation method based on GAs coupled to NNs was developed for experimental design of xylitol fermentation (Fig. 1).
Section snippets
Micro-organism, medium and culture conditions
Candida mogii ATCC 18364 used in this work was maintained on potato dextrose agar slants at 4 °C. The inoculum was prepared using (g dm−3): glucose, 20; xylose, 40; (NH4)2HPO4, 4; (NH4)2SO4, 1; KH2PO4, 4; MgSO4, 1; Bacto-yeast extract, 6 and Bacto-peptone, 6.5. The medium was autoclaved at 121 °C for 20 min after pH adjustment to 5 with 1 M NaOH at pH 5. The culture was grown in 300 cm3 shake-flasks with 170 cm3 medium at 200 rpm and 3 ° C for 48 h. After 20 min of sterile centrifugation at 3000
Medium optimisation
In parallel and standardised shake-flask experiments, medium optimisation was performed for four generations using the GA on the basis of the medium used by Chen et al. [17].
Fig. 2, Fig. 3 represent the course for each composition created by the GA in generation 0 and generation 3 for optimisation of xylitol fermentation by C. mogii. The concentration range is divided into 10 identical subunits, each of which represents the sum of the ‘individuals’ of 10 concentration levels.
In generation 0
Acknowledgements
This work was supported by grant No. 29776025 from NNSFC (National Natural Science Foundation of China) and No. C96068 from NSFFC (Natural Science Foundation of Fujian, China).
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