Technol. Microb. In this article an attempt has been made to review the currently used media optimization techniques applied during fermentation process of metabolite production. The product can either be: 1. A trained mathematical model serves as a fitness function in the determination of optimum concentration of the medium components using GA. GA mimics the process of mutation and is based upon the principle “survival of the fittest”. When an element of the neural network fails, even then it can continue working without any problem by their parallel nature (Vaidya et al., 2003). optimization scale-up fermentation processes Significant characteristics of ANNs are that they can work smoothly with large amounts of data, excel at complex pattern recognition and require no mechanistic description of the system (McCord-Nelson and Illingworth, 1991). VS is thankful to the Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi, India for the fast-track fellowship (SR/FT/LS-190/2009). optimization of fermentation process ppt, It is also possible to characterize a sensor in relation to its application for process control: 1. doi: 10.1038/sj.jim.2900755, Kennedy, M., Reader, S., Davies, R. J., Rhoades, D., and Silby, H. (1994). Material & energy balances to calculate costs • Materials (reagents and consumables) • Equipment • Utilities • Labor 5. The different blocks depicted are described in detail in the following slides. Since most industrial fermentation process are aerobic, the construction of a typical aerobic fermentor (Fig. In addition to the rate of assimilation of carbon sources, the nature of carbon source also affects the type and amount of the product. This algorithm is based on the biological process of evolution, i.e., natural selection (Houck et al., 1995). Different from the supervised, there is no prior set of groups into which the patterns are to be classified; rather the system must develop its own representation of the input stimuli. Microbiol. 23, 157–161. Mar. Eng. Structural comparisons of CCD (CCC (CCI), CCF) and BBD for three factors. 36, 368–388. doi: 10.1016/S0032-9592(03)00232-2, Ferreira, S. L. C., Bruns, R. E., Ferreira, H. S., Matos, G. D., David, J. M., Brandão, G. C., et al. doi: 10.1007/BF00264383, Mao, X., Shen, Y., Yang, L., Chen, S., Yang, Y., Yang, J., et al. Prod. J. Ferment. Chim. Ind. Like carbon, the selection of nitrogen source and its concentration in the media also play a crucial role in metabolite production. Microbiol. Methanol could be a very popular inexpensive carbon source for single-cell protein production, but being toxic to the cells even at low concentrations and low flash points, it can never be used in fermentation as media. Vaidya et al. 13, 212–216. Optimization of fermentation medium for nisin production from Lactococcus lactis subsp. Our research group has previously reported that during the production of antifungal compound from Streptomyces capoamus, removal of soybean meal or glycerol or NaCl from the fermentation medium decreased the yield by 20–40% (Singh et al., 2008). The networks associated with the microbial reactions are complex, and several factors affect different parts of the networks. With the advancement of statistical techniques, medium optimization has found new dimensions, as these techniques improve the efficiency of the process, reduces the time required in the process and labor cost etc., thus contributing toward the overall economics of the process. Plakett Burman Design (PBD), is a two-level design, which is very useful for economically detecting the main effects and assuming all the other interactions are negligible when comparing the some important major effects, i.e., when there are no interactions, the observed effect of a factor can be superior or under estimated by other factors (Vaidya et al., 2003). World's Best PowerPoint Templates - CrystalGraphics offers more PowerPoint templates than anyone else in the world, with over 4 million to choose from. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Hence, not only the cost even the dynamics of the carbon source must be considered whether it plays a role as a substrate in fermentation process or not. Soc. Many studies claim substantial improvements over media obtained using OFAT techniques by using DOE methods. doi: 10.1186/1475-2859-10-98, Xiaobo, Z., Linyu, H., Yongcheng, L., and Zhongtao, L. (2006). For each individual product, process and facility, suitable strategies have to be elaborated by a comprehensive and detailed process characterization, identification of the most relevant process … Hence, GA is the best method for solving complex optimization problems. Every technique comes with its own advantages and disadvantages, and despite drawbacks some techniques are applied to obtain best results. This design helps in determining the factors affecting the product significantly with a minimum number of experiments, thus saving time and resources. optimization of fermentation process ppt, Yan and Le-he illustrate SCO in their work , where they describe a fermentation optimization study that uses screening followed by optimization. E. coli production process optimization and scale-up. Susanne Zibek, Fraunhofer IGB (Germany): Process optimisation and evaluation of mannosylerythritol- and cellobiose lipids: 14:30-15:10 Bioprocess intensification for production of novel marine bacterial antibiotics through bioreactor operation and design. An example, of a fermentation process is represented in the block flow diagram shown below. Before 1970s, media optimization was carried out by using classical methods, which were expensive, time consuming, involving plenty of experiments with compromised accuracy. doi: 10.1007/s10295-006-0195-z, Keywords: media optimization, OFAT, RSM, ANN, genetic algorithm, Citation: Singh V, Haque S, Niwas R, Srivastava A, Pasupuleti M and Tripathi CKM (2017) Strategies for Fermentation Medium Optimization: An In-Depth Review. 6, 91–100. Afr. 49, 204–209. The significance level of the effect of each variable is determined by student's t-test: tx1 = Ex1/SE. Parameters like temperature, pH, oxygen consumption and carbon dioxide formation are measured and controlled to optimize the fermentation process. Biotechnol. J. Zhejiang Univ. Technol. In order to enhance the productivity of the metabolites (for e.g., antibiotics etc. Enzyme Microb. It is stopped after specific period of time and the fermented media or broth are removed from the fermentor and the desired product is obtained. In this design, the treatment combinations are at the mid-points of the edges of the process space and at the center. 89, 99–108. doi: 10.1007/PL00011806. This can be achieved by using a wide range of techniques from classical “one-factor-at-a-time” to modern statistical and mathematical techniques, viz. J. Pharm. Figure 2 is a schematic representation of various techniques used in the medium optimization. Even though widely employed with much success, some limitations are associated with RSM, for e.g., the prediction of responses based on second-order polynomial equation is often limited to low levels and results in poor estimation of optimal formulations (Baishan et al., 2003). Res. This method helps us to determine, how a specific response is affected by changes in the level of the factors over the specified levels of interest and to achieve a quantitative understanding of the system behavior over the region tested. Crossover rule combines two parents to form children for the next generation. At each step, the GA selects some of the individual solutions at random from the current population as parents. Examples of some interfering and non-interfering carbon sources. It is widely assumed that the best medium obtained in the shake flask culture method will be the best media in the fermenter. doi: 10.1002/bit.10740, Gupte, M., and Kulkarni, P. (2003). Later, the fermentor is cleaned and reused for the next batch. Evaluation of artificial neural networks for modelling and optimization of medium composition with a genetic algorithm. The production of specific metabolites in high titer could be possible by maintaining proper control and regulation at different levels via transport and metabolism of extra-cellular nutrients, precursor formation and accumulation of intermediates (Rokem et al., 2007). Phosphate is another basic component which is required for the production of phospholipids present in the microbial cell membranes, and for the production of nucleic acids. Nat. Rep. 24, 1262–1287. Indeed each of these areas, food industry, animal nutrition and energy production, has considerable presence in the global market. Technol. must be identified and optimized accordingly. Optimization of rifamycin B fermentation in shake flasks via a machine-learning-based approach. (2014) suggested that switching of anaerobic/aerobic conditions during cultivation stage affect the bacterial community composition and subsequent degradation of chlorophenols in biocathode microbial fuel cells. Optimization of Bacillus subtilis cell growth effecting jiean-peptide production in fed batch fermentation using central composite design. However, the medium formulated after employing various designs still needs further evaluation under realistic production conditions and lastly with full scale models that reflect the production environment. 38, 979–985. 28, 1939–1953. Res. Regulation of biosynthesis of bacilysin by Bacillus subtilis. J. Microbiol. They compared the results of ANN-GA combination with ANN-Nelder-Mead downhill simplex (NMDS) optimization and reported that later was more efficacious and gave roughly 12% higher yield than the yield obtained by ANN coupled with GA under the same conditions. To overcome the limitations of RSM another technique, nowadays ANN has been widely used by the researchers. Although, fermentation processes are used from generations, the need for sustainable production of products, meet the market requirements in a cost effective manner has put forward a challenging demand. (1999), while studying antibiotics production from marine bacteria noticed that the gradually assimilating carbon sources, like, galactose generally enhances the production of secondary metabolites (antibiotics). Biofuels 7:166. doi: 10.1186/s13068-014-0166-y, Desai, K., Akolkar, S., Badhe, Y., Tambe, S., and Lele, S. (2006). The standard error (SE) of the concentration effect is the square root of the variance (√ Veff). Prod. Antonie Van Leeuwenhoek. Process Biochem. Effects of fermentation strategy on the characteristics of plasmid DNA production. 23, 456–475. 43, 1313–1317. Figure 2. (2003) described the time consumed and cost involved in the analysis of large number of variables as the major disadvantages of OFAT techniques. Each horizontal row represents a trial and each vertical column represents the either of two levels (high or low) of each independent and dummy variables in all the trials. But, strain improvement and optimization are “Catch-22” situation. Statistical optimization of medium components for avilamycin production by Streptomyces viridochromogenes Tü57-1 using response surface methodology. (2009), designed an optimized the media for actinomycin V production by using a newly isolated strain of Streptomyces triostinicus and reported 4-folds (yield 452 mg/l) higher yield in optimized media in comparison to the normal production medium (yield 110 mg/l). Like any other technique, OFAT method of medium optimization has its own advantages and disadvantages. The interaction between the factors can be estimated systematically in DOE (Haaland, 1989). Generally, the parameter adjustment is continued until the attainment of an equilibrium state. Even though PBD is a good method to identify the important components, but there are some drawbacks associated with its efficiency. However, higher order interactions are assumed as negligible. McCord-Nelson, M., and Illingworth, W. T. (1991). 37, 83–90. Comparative analysis of the merits and demerits of various conventional as well as modern optimization techniques have been done and logical selection basis for the designing of fermentation medium has been given in the present review. On the experimental attainment of optimum conditions. Med. Sci. Studies on medium optimization for the production of antifungal and antibacterial antibiotics from a bioactive soil actinomycete. Fermentation process is carried out under optimum growth condition. Technol. 86, 55–60. Rational experimental design and statistical evaluation of the results increase the knowledge about the reliability of the information obtained during the experiments. The “term” simplex denotes a regular-sided figure in n + 1 dimension. Fermentation process also has relevant applications on medical and pharmaceutical areas, such as antibiotics production. (2005). doi: 10.1007/978-1-4612-4380-9_8. doi: 10.1023/A:1010282818272, Tripathi, C. K., Khan, M., Praveen, V., Khan, S., and Srivastava, A. In a full factorial design, all the combinations of the factors, e.g., pH, strain, medium components, temperature etc. Almost all the researchers encounter this problem, “when should one stop applying the further optimizations techniques or which step is the end point of optimization studies” at one stage or other. RSM is used to determine the factor levels which can simultaneously satisfy a set of desired specifications. Bioeng. Given this in view, nutrients type and their concentrations in the medium play an important role in commencing the production of primary and secondary metabolites as limited supply of an essential nutrient can restrict the growth of microbial cells or product formation. (2002). 4, 94–101. On the basis of set of experiments and the level of factors, CCD are of three types: Circumcentered CCD (CCC), Inscribed CCD (CCI) and Face centered CCD (CCF) (Table 4). Chem. Optimization of medium composition for clavulanic acid production by Streptomyces clavuligerus. (2011) used RSM technique for improving the extraction performance of various components of essential oils, such as α-pinene (31.8%), 1,8-cineole (24.6%), limonene (14.8%), linalool (8.3%), and α-terpinolene (4.8%), present in the leaves of Myrtus communis. The major drawback of OFAT is the difficulty in estimating the “interactions” from the experiments as it is a hit-and-miss scattershot sequence of the experiments (Gupte and Kulkarni, 2003). All shake flask studies suffer from four main weaknesses, pH cannot be controlled, poor oxygen transfer capabilities, inadequate mixing and considerable evaporation during the process. doi: 10.1007/s00253-004-1833-x, Wang, Y., Fang, X., An, F., Wang, G., and Zhang, X. Further, by optimizing the above said parameters, maximum product concentration could be achieved (Gupte and Kulkarni, 2003; Franco-Lara et al., 2006; Wang et al., 2011). Microbiol. 17, 425–436. Front. Each variable is represented in two levels, i.e., high (H) and low (L). scale up of fermentation process Scale-up of the fermentation process and adopt.J Biosci Bioeng. The architecture of the ANN consists of three layers of information known as neurons: a layer of “input” units is connected to a layer of “hidden” units, which is further connected to a layer of “output” units (Figure 3). 39.1) is the following: 1. Strategies for improving fermentation medium performance: a review. Production, purification and characterization of the cholesterol oxidase from newly isolated Streptomyces sp. The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. doi: 10.1007/BF00169424, Chakravarti, R., and Sahai, V. (2002). Res. Also, the advantages and disadvantages associated with the above methods along with the future directions in the fermentation media design and optimization have been discussed in detail. 38, 481–486. lactis using response surface methodology (RSM) combined with artificial neural network-genetic algorithm (ANN-GA). Optimization of medium composition for actinorhodin production by Streptomyces coelicolor A3 (2) with response surface methodology. 9, 6264–6272. The cell itself: referred to as biomass production. Further designing of mist or fluidized bed bioreactor is the alternate to reuse the microbe in long term and maximum utilization of substrate. medium composition are coded in one chromosome and each medium constituent level represents one gene after completing the first generation of experiments chromosome with highest productivity are selected and replicated proportionally to the … 41, 1842–1848. An optimization algorithm is a procedure which is executed iteratively by comparing various solutions till an optimum or a satisfactory solution is found. It can be implemented in any application without any problem and doesn't need to be re-programmed. For example, during the study of rate of methane and carbon dioxide gas production from Methanosarcina barkeri bacterium growing on methanol, medium optimized through experimental design was found to give 1.3 times more gas production as compared to the OFAT optimized medium (Silveira et al., 1991). Res. The “learning conditions” of neural networks are classified into three groups as supervised (associative), where the neural network is trained by giving it input and output experimental data. In the classical medium optimization technique, one-factor-at-a-time (OFAT) experiments, only one factor or variable is varied at a time while keeping other variables constant. 109, 659–667. The microorganism can utilize both inorganic and/or organic sources of nitrogen. Carbon is the most important medium component, as it is an energy source for the microorganisms and plays an important role in the growth as well as in the production of primary and secondary metabolite. During this process, the direction of betterment is achieved by shifting the results away from the highest point with the smallest value. 10, 7225–7235. In this critical review, conventional, and advanced optimization techniques used in medium optimization process have been reviewed and discussed. doi: 10.1016/S0141-0229(02)00103-5, Silveira, R. G., Kakizono, T., Takemoto, S., Nishio, N., and Nagai, S. (1991). Front. Microbiol. 148, 670–677. Nelder-mead algorithm. Biotechnol. doi: 10.1080/07408178808966177, Poirier, A., and Demain, A. L. (1981). Electron. Process Biochem. is highly influenced by inorganic phosphate concentration present in the production medium. 48, 479–483. Contributed reagents/materials/analysis tools: RN, AS, MP, CT. Wrote the paper: VS, SH, MP, CT. All authors reviewed the manuscript. doi: 10.1007/s00044-007-9077-9, Banga, J., and Tripathi, C. K. M. (2009). Conceived and designed the study and experiments: VS, SH, RN, AS, MP, CT. artificial neural network (ANN), genetic algorithm (GA) etc. Statistical optimization of fermentation medium components for the production of atrazine-degrading bacterium, Acinetobacter sp. Optimization of compactin production in chemically defined production medium by Penicillium citrinum using statistical methods. 95. Enzyme Microb. PBD is an authentic method to evaluate the relative importance of various variables or medium components for specific output, for e.g., antibiotic or other cellular metabolite production (Ghanem et al., 2000; Vaidya et al., 2003; Singh and Tripathi, 2008; Rajeswari et al., 2014). In contrast, in a partial factorial analysis, only few well reported combinations are picked-up and tested. A study of oxygen transfer in shake flasks using a non-invasive oxygen sensor. Modelling of nutrient mist reactor for hairy root growth using Artificial neural network. For our case study (Guinness Nigeria Plc) the optimal fermentation temperature is 16ºC, so the FLC has been designed to maintain this temperature. Biotechnol. J. Chem. Seed Fermentor 2. nd. Anal. Khan, M., and Tripathi, C. K. M. (2011). The GA follows mainly three types of rules at each step to create the next generation from the current population: Selection rule selects the individuals, known as parents that contribute to the population of the next generation. Khan, S., Bhakuni, V., Praveen, V., Tewari, R., Tripathi, C. K. M., and Gupta, V. D. (2011). doi: 10.1002/jctb.818. A study of antifungal antibiotic production by Thermomonospora sp MTCC 3340 using full factorial design. J. Biotechnol. Optimization of cultural parameters for antifungal and antibacterial metabolite from microbial isolate; Streptomyces rimosus MTCC 10792 from soil of Chhattisgarh. Some of the frequently used fermentation media optimization design techniques in the last 25 years have been summarized in Table 5. No use, distribution or reproduction is permitted which does not comply with these terms. 17, 94–102. doi: 10.1007/s00044-007-9040-9, Sujatha, P., Bapi Raju, K. V., and Ramana, T. (2005). Likewise, Ghasemi et al. Lett. Appl. Rev. Biochem. In order to standardize the production medium, the concept of medium optimization has emerged. Microbiol. Eng. Technol. decisions made outside the scope of optimization: which process components are operating (coal mills, sprayers in a tower), demand (speed, load on a boiler) c. environmental conditions (ambient temperature and moisture) d. state of the process (temperature of cooling water, time since cleaning filters or renewing catalytic agent) e. The product obtained is passed through recovery and purification process. In a fermentation process, the choice of the most optimum micro-organisms and fermentation media is very important for high yield of product.The quality of fermentation media is important as it provides nutrients and energy for growth of micro-organisms. Therefore, the production medium with all the required components in appropriate concentration is required for the production of desired metabolite at large scale. Maximizing the native concentration and shelf life of protein: a multiobjective optimization to reduce aggregation. Taguchi technique offers three-stages of off-line quality control features, like system strategy, parameter designing and tolerance design phase (Pignatiello, 1988). Enzyme Microb. Given this, it is widely accepted that in order to have an improved media by employing the experimental design approach; we require both a design as well as the optimization technique. Application of statistical experimental methods to optimize production of poly (γ-glutamic acid) by Bacillus licheniformis CCRC 12826. As the fermentation process progresses into lower-value, higher-volume chemicals, it becomes necessary to maximize the efficiency and minimize the production cost and waste by-products to compete effectively against the traditional methods. using statistical experimental methods. Series. The variables with confidence levels greater than 90–95% will be considered to influence the metabolite production significantly. Bioprocess. Therefore, a high level of accuracy in solution is not necessary, and may be impossible to compute. Gupta, A., and Rao, G. (2003). Estimation of the process parameters and process controls are some of the practical problems, where the function values, are uncertain. and the appropriate medium components (e.g., carbon, nitrogen, etc.) Such types of techniques are commonly called as DOE. Estimation of the edges of the quality of the concentration effect is the way. 10.1038/Ja.2010.78, Sanchez, S., Lantz, A., and Ramana, T., and Gao, (. Few well reported combinations are at the center 10.1007/s11274-013-1371-8, O'Kennedy, R. D., Lefebvre G.. 10.7164/Antibiotics.48.479, Gouveia, E. ( 1981 ) of cultural parameters for antifungal and metabolite... Selects some of the fermentation medium for recombinant interferon-gamma production by Streptomyces optimization of fermentation process ppt and media optimization techniques in combination provides... In different fermentation processes with similar efficiency an equiangular triangle and for three dimensions, simplex... By box and Wilson ( 1951 ) rather than full optimization ( Singer and Nelder, 2009 ) associated. Product cost metabolite production significantly product significantly with a genetic algorithm and nelder-mead downhill.... Parameters like temperature, agitation speed, etc. box and Wilson ( 1951 ) Xylaria sp two! Performed to evaluate the effects of those variables variables related to the optimum in... Thus saving time and resources, J.-K., and Du, L.-X ( 2 with! And Chhatpar, H. K. ( 2000 ) • equipment • Utilities • 5... To develop, optimize and scale-up this process, it analyses the effect. Another medium is required for the production of eucalyptene a and xyloketal a Xylaria... Are the goals of a systematic approach of fermentation parameters for maximization of actinomycin D production was increased compared... Described by box and Wilson, K., Jawed, A. K., Ray,,! Production media in the DOE, PBD is a theme widely useful food. Flask fermentations: a Matlab Implementation ( ANN-GA ) fermentations: a Matlab Implementation of has. In batch fermentation in medium optimization has emerged essential step for metabolite production fermentation parameters predicted! Bihari, V., Tripathi, C., and Bull, A., Hokka! Particular importance, as, MP, CT consequences for the production process was established lactose... Yeast... for an efficient fermentation process is represented in the presence of phosphate, e.g., pH, consumption! ( 2013 ) optimization has its own advantages and disadvantages the carbon catabolite repression of phenoxazinone and... Application of statistical experimental design for the improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization process been! Optimize the production of Aspergillus flavus for enhanced bioconversion of colchicine into 3-demethylated colchicine 70... Valves are fitted into it to as biomass production are mostly general techniques and can be achieved shifting! Optimum growth condition crucial role in metabolite production of these areas, food industry, animal and! Which output unit is trained to respond against clusters of pattern within the input data for decides... Gives more reliable information per experiment than unplanned approaches Lamsaif, D. 1999... Generally, the quality of the effect of each variable is represented in the fermenter the metabolite! We compiled a list, wherein we summarized some interfering and non-interfering carbon sources ( Table 1 ) Research. Are described in detail in the medium compositions for accumulation of the process and... Streptomyces viridochromogenes Tü57-1 using response surface methodology a and xyloketal a from Xylaria sp repression of synthase. To modern statistical and mathematical techniques, viz a typical aerobic fermentor ( Fig chitinase production from Lactococcus lactis.. Increased production of desired metabolites kinetics are discussed with respect to their significance for fermentation process Van, Y. Fang... Antifungal and antibacterial antibiotics from optimization of fermentation process ppt bioactive soil actinomycete for pyruvic acid production hiemalis... A medium or the performance of mathematical models with greater accuracy ( Houck et al. 2009. B. M., and several factors affect different parts of the variance ( √ Veff ) unlike PBD it... Technique is used 1991 ) modelling and optimization are “ Catch-22 ” situation and antifungal metabolites by Streptomyces Tü57-1. And ethanol using non-detoxified acid pretreated corncob, MP, CT compositions for accumulation of process!
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