Commentary: Bioprocessing and the essentials of biochemistry
1
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
While the media might portray the essence of the Biotechnology industry as a direct route from DNA to an effective biopharmaceutical, we understand that it is somewhat more complex. What distinguishes the life sciences industry from traditional pharmaceutical development is that in Biotechnology, it often requires a living system to produce a therapeutically effective product. Examining what initiated the modern bioscience industry (commercial production of insulin and erythropoietin for example) makes it clear that the industry was founded through producing previously known and well-characterized biomolecules efficiently enough to become commercially viable and reproducibly enough to meet the rigorous requirements of regulatory agencies such as the US Food and Drug Administration. The complexity of manipulating living systems for industrial purposes might have had roots as early as the production of bread, beer, and wine, but today's life sciences industry requires vastly more precision and sophistication. The complexity of higher order protein structure and often problematic stability make for challenging issues of production and quality control. Not to take anything from the fermentation skill of a vintner of fine wine, but there is no tolerance for a difference in “vintage” for our biopharmaceuticals—they must be exactly the same every time for every patient. The commercial production of recombinant hormones, peptides, growth factors, monoclonal antibodies, and vaccines has been increasing at a rapid pace, providing benefit for sufferers of numerous diseases. As a result, within the industry there has been much discussion of the impending shortage of production facilities. The physical facilities required to produce biomolecules involve long lead times and enormous capital to design, build, and validate. Less is heard regarding an equally difficult, expensive, and time consuming challenge: having enough sufficiently educated people who not only appreciate the engineering challenges required to make a GMP (Good Manufacturing Practices) facility, but who also understand the basic principles of biochemistry, cell biology, and structural biology. It makes little sense to invest in expensive facilities that will produce biopharmaceuticals if there will not be enough sufficiently trained people to operate and manage them. More importantly, however, if we cannot produce the molecules that will cure and prevent disease, we deny the benefits of our science to society. If our students are to participate in the production of new biomolecules, it is imperative that we review our Biochemistry and Molecular Biology curricula to assure the proper balance of recombinant DNA technologies with structural biology and physical methods, especially in regards to protein structure and function. There is already far too much material to teach in most of our courses so it will take an active discussion among academic disciplines to work out strategies for teaching the basics effectively. However, there must be time within our curricula to include a complete survey of protein purification technologies, physical methods of structural analysis, and kinetic methods for quantitative analysis of enzymatic activities. My informal and unscientific survey of course material reveals a decreasing proportion of Biochemistry and Molecular Biology courses devoted to the “old fashioned” principles of protein chemistry. However, it is essential that our students understand the basic principles of protein purification and the criteria used to establish the meaning of “pure.” They must have at least an appreciation of the power and limits of the technologies employed to determine protein structure, purity, and function. This will include spectroscopic and physical methods that are the underlying technologies used in the industry, from Raman spectroscopy to differential scanning calorimetry. While it will not be easy to fit these into curricula already jammed with important molecular concepts that are expanding every day, it must be actively discussed, and then appreciated as foundational material. It might not be important to know how a particular protein is purified; only that it functions as predicted as a treatment. That is true enough if all you want to do is be a user of the product. The real opportunity to effect change and to benefit from it optimally comes to those who develop, understand, and control the technology. The people who have this power will be those who understand how to produce the wonderful products yet to come. They should be our students.Keywords:
Biopharmaceutical
Pace
Cite
Bioprocess engineering
Process design
Metabolic Engineering
Cite
Citations (61)
Bioprocess engineering
Cite
Citations (7)
The production and storage of energy from renewable resources steadily increases in importance. One opportunity is to utilize carbon dioxide (CO2)-type hydrogenotrophic methanogens, which are an intriguing group of microorganisms from the domain Archaea, for conversion of hydrogen and CO2 to methane (CH4). This review summarizes the current state of the art of bioprocess development for biological CH4 production (BMP) from pure cultures with pure gasses. The prerequisites for successful quantification of BMP by using closed batch, as well as fed-batch and chemostat culture cultivation, are presented. This review shows that BMP is currently a much underexplored field of bioprocess development, which mainly focuses on the application of continuously stirred tank reactors. However, some promising alternatives, such as membrane reactors have already been adapted for BMP. Moreover, industrial-based scale-up of BMP to pilot scale and larger has not been conducted. Most crucial parameters have been found to be those, which influence gas-limitation fundamentals, or parameters that contribute to the complex effects that arise during medium development for scale-up of BMP bioprocesses, highly stressing the importance of holistic BMP quantification by the application of well-defined physiological parameters. The much underexplored number of different genera, which is mainly limited to Methanothermobacter spp., offers the possibility of additional scientific and bioprocess development endeavors for the investigation of BMP. This indicates the large potential for future bioprocess development considering the possible application of bioprocessing technological aspects for renewable energy storage and power generation.
Chemostat
Bioprocess engineering
Cite
Citations (125)
Microbial biosurfactants are currently emerging as fully bio-based and renewable alternatives to traditional petroleum-based surfactants. The yeast Starmerella bombicola is a known producer of glycolipid surfactants and through genetic engineering, the portfolio of biosurfactants has been expanded towards new innovative compounds such as the bolaform sophorosides. Despite their interesting properties and potential applications, the low productivities of their biosyntheses currently do not allow the process to be economically viable. In this work, the bottlenecks leading to low productivities will be tackled through bioprocess development. Typically such bioprocess development is combined with targeted and off-line analyses of substrates and bioproducts. However, these analyses do not provide any information about unknown underlying biochemical ‘marker’ pathways/metabolites influencing biosurfactant production. Additionally, the off-line and delayed follow-up often results in measures not taken timely. Therefore, a metabolomics approach to monitor the fermentation in real-time will be set up in parallel to the bioprocess development. The metabolic fingerprint of fermentations will be monitored by using an untargeted automated laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) platform and correlated to the bioprocess efficiency. This metabolomics approach, reflective of the complex interplay between microbial kinetics and dynamic environmental changes in bioreactors, will speed up bioprocess development. Moreover, a successful at-line metabolomics approach would be a powerful tool in the monitoring of (industrial) fermentations.
Bioproducts
Bioprocess engineering
Cite
Citations (0)
Abstract The advancement of bioprocess monitoring will play a crucial role to meet the future requirements of bioprocess technology. Major issues are the acceleration of process development to reduce the time to the market and to ensure optimal exploitation of the cell factory and further to cope with the requirements of the Process Analytical Technology initiative. Due to the enormous complexity of cellular systems and lack of appropriate sensor systems microbial production processes are still poorly understood. This holds generally true for the most microbial production processes, in particular for the recombinant protein production due to strong interaction between recombinant gene expression and host cell metabolism. Therefore, it is necessary to scrutinise the role of the different cellular compartments in the biosynthesis process in order to develop comprehensive process monitoring concepts by involving the most significant process variables and their interconnections. Although research for the development of novel sensor systems is progressing their applicability in bioprocessing is very limited with respect to on-line and in-situ measurement due to specific requirements of aseptic conditions, high number of analytes, drift, and often rather low physiological relevance. A comprehensive survey of the state of the art of bioprocess monitoring reveals that only a limited number of metabolic variables show a close correlation to the currently explored chemical/physical principles. In order to circumvent this unsatisfying situation mathematical methods are applied to uncover "hidden" information contained in the on-line data and thereby creating correlations to the multitude of highly specific biochemical off-line data. Modelling enables the continuous prediction of otherwise discrete off-line data whereby critical process states can be more easily detected. The challenging issue of this concept is to establish significant on-line and off-line data sets. In this context, online sensor systems are reviewed with respect to commercial availability in combination with the suitability of offline analytical measurement methods. In a case study, the aptitude of the concept to exploit easily available online data for prediction of complex process variables in a recombinant E. coli fed-batch cultivation aiming at the improvement of monitoring capabilities is demonstrated. In addition, the perspectives for model-based process supervision and process control are outlined.
Process Analytical Technology
Cite
Citations (124)
Commodity chemicals
Metabolic Engineering
Bioprocess engineering
Cite
Citations (50)
Bioprocess engineering
Cite
Citations (0)
This review is related to bioreactors for plant suspension culture and its products. Bioreactor plays an important role in bioprocess engineering. The core of bioprocessing technology is the bioreactor. A bioreactor is basically a device in which the organisms are cultivated and helps in production of desired products in a contained environment. Bioreactors are usually a containment which provides optimal condition for microorganisms in order to produce desired products. In this review, the bioreactor’s principle, working and its types are discussed. Enclosed by unit operations that carry out physical changes for medium preparation and recovery of products, the reactor is where the major chemical and biochemical transformations occur. In many bioprocess, characteristic of the reaction determined to a large extent the economic feasibility of the project. The integration of biosynthesis and separation is considered as a possible approach towards more efficient plant cell and tissue culture. In this review article, the aspects of bioprocess engineering for plant suspension culture and its products, bioreactor types, optimized strategies for production of secondary metabolites also and its industrial applications.
Bioprocess engineering
Suspension culture
Suspension
Cite
Citations (9)
Cyanobacteria have the potential to become an industrially sustainable source of functional biopolymers. Their exopolysaccharides (EPS) harbor chemical complexity, which predicts bioactive potential. Although some are reported to excrete conspicuous amounts of polysaccharides, others are still to be discovered. The production of this strain-specific trait can promote carbon neutrality while its intrinsic location can potentially reduce downstream processing costs. To develop an EPS cyanobacterial bioprocess (Cyano-EPS) three steps were explored: the selection of the cyanobacterial host; optimization of production parameters; downstream processing. Studying the production parameters allow us to understand and optimize their response in terms of growth and EPS production though many times it was found divergent. Although the extraction of EPS can be achieved with a certain degree of simplicity, the purification and isolation steps demand experience. In this review, we gathered relevant research on EPS with a focus on bioprocess development. Challenges and strategies to overcome possible drawbacks are highlighted.
Cite
Citations (73)
Abstract A systematic concept in bioprocess analysis and design is presented according to an integrating strategy as basis for a biotechnological methodology. A comparison illustrates analogies and significant differences between chemical and biological processes. The study of the interactions between environments and organisms includes influences of physical transport phenomena and also enzyme and metabolic regulations. In both cases the macroscopic principle with a formalkinetic approach is recommended for quantification purposes. The determination of the characteristic‐time‐regime with characteristic rate constants makesit possible to simplify mathematical modeling using the concepts of the rate‐determining‐step and quasistationarity. Finally, guidelines are summarized for the use of unstructured and structured kinetic models.
Basis (linear algebra)
Cite
Citations (6)