Latest Research on Fermentation processes : Mar 2022

Improvement of microbial strains and fermentation processes

Improvement of microbial strains for the over-production of industrial products has been the hallmark of all commercial fermentation processes. Conventionally, strain improvement has been achieved through mutation, selection, or genetic recombination. Over-production of primary or secondary metabolites is a complex process, and successful development of improved strains requires a knowledge of physiology, pathway regulation and control, and the design of creative screening procedures. In addition, it requires mastery of the fermentation process for each new strain, as well as sound engineering know-how for media-optimization and the fine-tuning of process conditions. This review focuses on the various options that may be employed to improve microbial strains and addresses the complex problems of screening, the tools and technology behind the selection of targeted organisms, and the importance of process optimization. Furthermore, this review discusses new and emerging technologies and designing optimized media for tracking mutants with enhanced productivity or other desired attributes.[1]


Metabolic regulation of fermentation processes

To compete in nature against other forms of life, microorganisms possess regulatory mechanisms which control production of their metabolites, thus, protecting against overproduction and excretion of these primary and secondary metabolites into the environment. To effect such an economical form of life, they possess regulatory mechanisms which control production of these metabolites and protect against overproduction and excretion into the environment of excess concentrations. In the field of industrial fermentation, the opposite concept prevails. Fermentation microbiologists search for a rare overproducing strain in nature, then further deregulate the microorganism so that it overproduces huge quantities of a desired commercially important product such as a metabolite or an enzyme. Deregulation is brought about by nutritional as well as classical and molecular genetic manipulations to bypass and/or remove negative regulatory mechanisms and to enhance positive regulatory mechanisms. These mechanisms include induction, nutritional regulation by sources of carbon, nitrogen and phosphorus, and feedback control. The controls and their modification by biotechnologists are the subjects of this review.[2]


Optimization and scale up of industrial fermentation processes

To increase product yields and to ensure consistent product quality, key issues of industrial fermentations, process optimization and scale up are aimed at maintaining optimum and homogenous reaction conditions minimizing microbial stress exposure and enhancing metabolic accuracy. 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 parameters influencing product yield and quality and their establishment as scale-up parameters to be kept constant as far as possible. Physical variables, which can only be restrictedly kept constant as single parameters, may be combined with other pertinent parameters to appropriate mathematical groups or dimensionless terms. Process characterization is preferably based on real-time or near real-time data collected by in situ and on-line measurements and may be facilitated by supportive approaches and tools like neural network based chemometric data analysis and modelling, clarification of the mixing and stream conditions through computational fluid dynamics and scale-down simulations. However, as fermentation facilities usually are not strictly designed according to scale-up criteria and the process conditions in the culture vessels thus may differ significantly and since any strategy and model can only insufficiently consider and reflect the highly complex interdependence and mutual interaction of fermentation parameters, successful scale up in most cases is not the result of a conclusive and straight-lined experimental strategy, but rather will be the outcome of a separate process development and optimization on each scale. This article gives an overview on the problems typically coming along with fermentation process optimization and scale up, and presents currently applied scale-up strategies while considering future technologies, with emphasis on Escherichia coli as one of the most commonly fermented organisms.[3]


Optimizing scale-up fermentation processes

There are many aims associated with the optimization of fermentation processes. Optimization is expected to increase the yield of the final product but the process must be compliant with good manufacturing practices, the available equipment and the expected final scale of operation. Dealing with genetically modified microorganisms that overproduce recombinant protein has the advantage that the vast majority of the processes use only three different species, namely Escherichia coli, Saccharomyces cerevisiae and Pichia pastoris. Standard processes for each organism are described in textbooks and serve as a basis for the development of a tailored process. This article outlines the general philosophy that we have devised to ensure an efficient approach of scaling up fermentation processes for biopharmaceutical purposes, in a multidisciplinary environment.[4]


Recent advances in lactic acid production by microbial fermentation processes

Fermentative production of optically pure lactic acid has roused interest among researchers in recent years due to its high potential for applications in a wide range of fields. More specifically, the sharp increase in manufacturing of biodegradable polylactic acid (PLA) materials, green alternatives to petroleum-derived plastics, has significantly increased the global interest in lactic acid production. However, higher production costs have hindered the large-scale application of PLA because of the high price of lactic acid. Therefore, reduction of lactic acid production cost through utilization of inexpensive substrates and improvement of lactic acid production and productivity has become an important goal. Various methods have been employed for enhanced lactic acid production, including several bioprocess techniques facilitated by wild-type and/or engineered microbes. In this review, we will discuss lactic acid producers with relation to their fermentation characteristics and metabolism. Inexpensive fermentative substrates, such as dairy products, food and agro-industrial wastes, glycerol, and algal biomass alternatives to costly pure sugars and food crops are introduced. The operational modes and fermentation methods that have been recently reported to improve lactic acid production in terms of concentrations, yields, and productivities are summarized and compared. High cell density fermentation through immobilization and cell-recycling techniques are also addressed. Finally, advances in recovery processes and concluding remarks on the future outlook of lactic acid production are presented.[5]


Reference

[1] Parekh, S., Vinci, V.A. and Strobel, R.J., 2000. Improvement of microbial strains and fermentation processes. Applied microbiology and biotechnology, 54(3), pp.287-301.

[2] Sanchez, S. and Demain, A.L., 2002. Metabolic regulation of fermentation processes. Enzyme and Microbial Technology, 31(7), pp.895-906.

[3] Schmidt, F.R., 2005. Optimization and scale up of industrial fermentation processes. Applied microbiology and biotechnology, 68(4), pp.425-435.

[4] Thiry, M. and Cingolani, D., 2002. Optimizing scale-up fermentation processes. TRENDS in Biotechnology, 20(3), pp.103-105.

[5] Abdel-Rahman, M.A., Tashiro, Y. and Sonomoto, K., 2013. Recent advances in lactic acid production by microbial fermentation processes. Biotechnology advances, 31(6), pp.877-902.

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