Optimization Of Downstream Processing Research Articles

Microbial Bioherbicides Based on Cell-Free Phytotoxic Metabolites: Analysis and Perspectives on Their Application in Weed Control as an Innovative Sustainable Solution.

Weeds cause significant agricultural losses worldwide, and herbicides have traditionally been the main solution to this problem. However, the extensive use of herbicides has led to multiple cases of weed resistance, which could generate an increase in the application concentration and consequently a higher persistence in the environment, hindering natural degradation processes. Consequently, more environmentally friendly alternatives, such as microbial bioherbicides, have been sought. Although these bioherbicides are promising, their efficacy remains a challenge, as evidenced by their limited commercial and industrial production. This article reviews the current status of microbial-based bioherbicides and highlights the potential of cell-free metabolites to improve their efficacy and commercial attractiveness. Stirred tank bioreactors are identified as the most widely used for production-scale submerged fermentation. In addition, the use of alternative carbon and nitrogen sources, such as industrial waste, supports the circular economy. Furthermore, this article discusses the optimization of downstream processes using bioprospecting and in silico technologies to identify target metabolites, which leads to more precise and efficient production strategies. Bacterial bioherbicides, particularly those derived from Pseudomonas and Xanthomonas, and fungal bioherbicides from genera such as Alternaria, Colletotrichum, Trichoderma and Phoma, show significant potential. Nevertheless, limitations such as their restricted range of action, their persistence in the environment, and regulatory issues restrict their commercial availability. The utilization of cell-free microbial metabolites is proposed as a promising solution due to their simpler handling and application. In addition, modern technologies, including encapsulation and integrated management with chemical herbicides, are investigated to enhance the efficacy and sustainability of bioherbicides.

Innovations in algal biorefineries for production of sustainable value chain biochemicals from the photosynthetic cell factories

The concept of biorefinery can explore and expand new dimensions of bio-based commodity production, which will be crucial for sustainable economic growth. A biorefinery is likely to transform biomass into renewable energy and bioenergies for human wellbeing, such as pigments, proteins and biopolymers. Photosynthetic biomass (plant and algae-based), utilized atmospheric CO2 fixation and cheaper substrates (industrial byproducts) with simultaneous production of high value renewables (HVRs). However, due to their high potential of CO2 sequestration, utilization of wastewaters, algae could be considered a potential candidate as compared to terrestrial plants. In addition, pretreatment of algal biomass, its conversion and utilization are cheaper as compared to lignocellulosic waste. Techniques such as gasification, torrefaction, hydrothermal liquefaction can be utilized for the generation of bio-oil/biocrude, syngas, ash, and others, which can effectively be used for fuels and HVRs, respectively. Further, algal cultivation can also pose a potential advantage in terms of a zero-waste biorefinery as algal biomass consists of various proteins, lipids, carbohydrates, pigments and other bioactive components that can be utilized is different industrial sectors including cosmetics, nutraceuticals, and pharmaceuticals. However, alternative technology is required to reduce their production and extraction cost, where resources need to be utilized in a sustainable manner. In this context, the usage of some recyclable solvents such as green-solvents/ionic liquids to extract bioactive components without the cell disruption can acts as an effective technology for improving the algal biorefinery. Such “milking” technologies need further optimization of downstream processes to make it cost-effective. Similarly, for the upstream microalgal cultivation, biorefinery approach can combined with wastewater treatment/ bioremediation and GHG sequestration/ flue gas supplementation can be a promising approach to reduce the production cost. Therefore, with these advancements, an algal biorefinery can efficiently generate higher revenues. In this review, we discuss various upstream and downstream processing strategies and the potential possibilities, challenges and future perspectives of an algal biorefinery system has been discussed.

Rheology of microalgae concentrates and its influence on the power consumption of enzymatic hydrolysis processing

The optimization of downstream processing is a critical step in any microalgae-related process. The microalgal biomass is separated from the initial diluted cultures to form a concentrated slurry, the properties of which greatly influence the design and performance of further processing steps, such as enzymatic hydrolysis. In this work, the rheological behaviour of two microalgal concentrates produced both in freshwater (Scenedesmus almeriensis) and seawater (Nannochloropsis gaditana) were studied. Measurements were performed on the entire range of biomass concentrations, from 0.5 g/L to 264 g/L. Non-Newtonian behaviour was observed whatever the water type and biomass concentration used, especially at high biomass concentrations above 10 g/L. The rheological data were adjusted to the Power Law model, and the consistency and flow behaviour indexes were correlated with the biomass concentration. The results show that the freshwater and seawater biomasses exhibited different behaviours, with freshwater slurries being more viscous than seawater ones. The high viscosity of freshwater slurries requires increased energy consumption for mixing, with an estimated cost increase of 60% when using them under the non-Newtonian conditions considered. These findings highlight the considerable effect of algal biomass rheology on the mixing power required during microalgal biomass processing.

Spherical nanoparticles can be used as non-penetrating tracers to determine the extra-particle void volume in packed-bed chromatography columns

The optimization of downstream processing in silico can accelerate bioprocess development by limiting experiments to the most promising separation conditions that have been identified using chromatography models. Such models describe protein binding and mass transport in packed-bed columns and thus require precise knowledge about the columns and the resins they contain. One important set of properties is the resin porosities, often determined using combinations of penetrating and non-penetrating tracers. However, the former can be disproportionately small, providing data of limited practical relevance, and the latter can undergo unwanted interactions with the resin, interfering with porosity calculations. Here we characterize and minimize the interactions of three novel hard-sphere non-penetrating tracers with the model resin Q Sepharose HP under various conditions and determine the corresponding inter-particle porosities. We found that conductivities > 100 mS cm−1 were necessary to suppress tracer–resin interactions despite them sharing the same surface charge. We combined these data with those from proteins studied under non-binding conditions, which can be used as authentic penetrating tracers, to determine both the intra-particle and total porosities. Furthermore, we found that the inter-particle porosity was below the theoretical limit of dense sphere packing (25.95%) and provide experimental data showing that the discrepancy is caused by resin particle deformation during the packing of columns under pressure.

Power-to-Protein: Carbon Fixation with Renewable Electric Power to Feed the World

Akanksha Mishra is currently a PhD student at the University of Tubingen in Germany. She is working in the field of gas fermentation under the supervision of Prof. Angenent. For her thesis, she is developing the power-to-protein system by operating a two-stage bioprocessing system. She is originally from India and moved to Germany after the completion of her undergraduate studies in biotechnology. She obtained a master’s degree in applied environmental geosciences also at the University of Tubingen. Dr. Jean Nepomuscene Ntihuga is a post-doctoral research associate at University of Tubingen, Germany in the Environmental Biotechnology Group at the Center of Applied Geosciences. He conducts research on chain elongation, especially in downstream process optimization. He worked on designing bioreactors during his doctoral research at the University of Hohenheim. With a background in chemical engineering, his research focused on application of engineering principles in the conversion of wastes to useful products and its impact on the environment. His goal is to help alleviate poverty and climate change mitigation through scale-up of developed processes and its application in decentralized systems. Dr. Bastian Molitor studied biology at the Ruhr University Bochum, Germany, where he also obtained his PhD. Afterward, he worked as a postdoctoral researcher at the RWTH Aachen University, before he moved on to a two-year research stay at Cornell University. Since 2017, Dr. Molitor has been a group leader at the University of Tubingen. His research focuses on the utilization of anaerobic gas-fermenting microbes for biotechnology. He studies the potential to genetically engineer acetogenic bacteria and methanogenic archaea, as well as the integration of bioprocesses with non-genetically engineered microbes to extend the product spectrum of gas fermentation. Prof. Dr. Ir. Largus Angenent leads the Environmental Biotechnology Group at the Center of Applied Geosciences at the University of Tubingen (Germany), where he holds a Humboldt Professorship. His group studies the recovery of carbon from wastewaters and industrial off gases with bioprocessing. The microbial catalysts can be pure cultures (including genetic modification), defined mixed cultures, or open cultures (microbiomes). His group also studies extracellular electron transfer, and he was one of the founding members of ISMET. Angenent is an expert on gas fermentation and chain elongation, and he started companies in these areas (Electrochaea, GmbH and Capro-X, Inc.).

Hydrophobin-Protein A Fusion Protein Produced in Plants Efficiently Purified an Anti-West Nile Virus Monoclonal Antibody from Plant Extracts via Aqueous Two-Phase Separation.

The development of monoclonal antibodies (mAbs) has provided vast opportunities to treat a wide range of diseases from cancer to viral infections. While plant-based production of mAbs has effectively lowered the upstream cost of mAb production compared to mammalian cell cultures, further optimization of downstream processing, especially in extending the longevity of Protein A resin by an effective bulk separation step, will further reduce the overall prohibitive cost of mAb production. In this study, we explored the feasibility of using aqueous two-phase separation (ATPS) in capturing and separating plant-made mAbs from host proteins. Our results demonstrated that an anti-West Nile virus mAb (E16) was efficiently separated from most plant host proteins by a single ATPS step, comprising the mixing of plant extracts containing Hydrophobin-Protein A fusion protein (HPA) and E16 and the subsequent incubation with an inexpensive detergent. This simple ATPS step yielded a highly enriched E16 mAb preparation with a recovery rate comparable to that of Protein A chromatography. The ATPS-enriched E16 retained its structural integrity and was fully functional in binding its target antigen. Notably, HPA-based ATPS was also effective in enriching E16 from plant host proteins when both HPA and E16 were produced in the same leaves, supporting the potential of further streamlining the downstream purification process. Thus, ATPS based on plant-produced HPA in unpurified extract is a cost-effective yet efficient initial capture step for purifying plant-made mAbs, which may significantly impact the approach of mAb purification.

Adsorption Characteristics of Human Immunoglobulin G on Five New Tetrapeptide Biomimetic Affinity Resins

Alternative antibody-binding affinity ligands are expected to support robust time- and cost-effective antibody purification with rapid improvement of upstream productivity and demand on downstream process optimization. Five new tetrapeptide biomimetic affinity ligands (FYRH, HWRH, YHRI, HYRF, and FHRA) were screened by modeling the molecular interaction mechanism between tetrapeptide ligands and the Fc fragment of IgG with molecular dynamics simulation and the flexible docking method, and the corresponding five resins were prepared in this work to evaluate their adsorption characteristics of human immunoglobulin G (hIgG). The results showed that the binding capacities to hIgG of the five resins showed a strong pH-dependency, which was high at pH 7.0–9.0, and extremely low at pH 5.0–6.0, providing a benefit choice to separate hIgG. The dynamic binding capacities (DBC) at 10% breakthrough of five resins could reach up to 28–37 mg/mLgel, and Ac-FYRH-4FF resin showed the best adsorption performance. The eluti...

Metabolic profiling as a tool for prioritizing antimicrobial compounds.

Metabolomics is an analytical technique that allows scientists to globally profile low molecular weight metabolites between samples in a medium- or high-throughput environment. Different biological samples are statistically analyzed and correlated to a bioactivity of interest, highlighting differentially produced compounds as potential biomarkers. Here, we review NMR- and MS-based metabolomics as technologies to facilitate the identification of novel antimicrobial natural products from microbial sources. Approaches to elicit the production of poorly expressed (cryptic) molecules are thereby a key to allow statistical analysis of samples to identify bioactive markers, while connection of compounds to their biosynthetic gene cluster is a determining step in elucidating the biosynthetic pathway and allows downstream process optimization and upscaling. The review focuses on approaches built around NMR-based metabolomics, which enables efficient dereplication and guided fractionation of (antimicrobial) compounds.

Domain antibody downstream process optimization: High‐throughput strategy and analytical methods

Application of scale‐down high‐throughput screening has become integral for process development of antibody therapeutic products. In this work, methods are described for using high‐throughput techniques to develop a multicolumn chromatography purification protocol for a small domain antibody with very limited material (<200 mg). Screenings utilized resin slurry plates to explore and narrow potential operating space, and miniature columns were used to either confirm operating spaces or further explore impurity separations. Lab scale column confirmations were performed when appropriate. Affinity capture chromatography as well as ion exchange and multimodal polishing chromatography steps were explored. Feedstreams were pooled and recycled to preserve material for the different chromatography steps. Precise high‐throughput analytical assays were developed to fully characterize the domain antibody to a similar extent as a typical commercial therapeutic protein program. Optimized two‐column and three‐column processes provided overall chromatography yields of 66 and 58%, respectively, and were able to meet typical early phase requirements for removal of impurities such as aggregates, host cell protein, endotoxin, and other product‐related impurities. This study provides a comprehensive example of how a thorough biologics downstream process can be developed with a minimum of material.

High-throughput micro-scale cultivations and chromatography modeling: Powerful tools for integrated process development.

Upstream processes are rather complex to design and the productivity of cells under suitable cultivation conditions is hard to predict. The method of choice for examining the design space is to execute high-throughput cultivation screenings in micro-scale format. Various predictive in silico models have been developed for many downstream processes, leading to a reduction of time and material costs. This paper presents a combined optimization approach based on high-throughput micro-scale cultivation experiments and chromatography modeling. The overall optimized system must not necessarily be the one with highest product titers, but the one resulting in an overall superior process performance in up- and downstream. The methodology is presented in a case study for the Cherry-tagged enzyme Glutathione-S-Transferase from Escherichia coli SE1. The Cherry-Tag™ (Delphi Genetics, Belgium) which can be fused to any target protein allows for direct product analytics by simple VIS absorption measurements. High-throughput cultivations were carried out in a 48-well format in a BioLector micro-scale cultivation system (m2p-Labs, Germany). The downstream process optimization for a set of randomly picked upstream conditions producing high yields was performed in silico using a chromatography modeling software developed in-house (ChromX). The suggested in silico-optimized operational modes for product capturing were validated subsequently. The overall best system was chosen based on a combination of excellent up- and downstream performance.

Optimization of upstream and downstream process parameters for cellulase-poor-thermo-solvent-stable xylanase production and extraction by Aspergillus tubingensis FDHN1

Abstract Background Xylanases are important members of the hemicellulolytic enzyme system. Xylanase plays a vital role in the hydrolysis of major hemicellulosic component xylan and converts it into xylooligosaccharides and ultimately yields xylose. Cellulase-lacking or cellulase-poor xylanase with high temperature and pH stability has gained special attention, especially in paper and pulp industries. Most of the available literature highlighted the fungal xylanase production by optimizing environmental and cultural parameters. However, the importance of enzyme recovery from fermented biomass still needs attention. In this study, upstream and downstream process parameters were studied for enhancing xylanase production and extraction by a newly isolated Aspergillus tubingensis FDHN1 under solid-state fermentation using low-cost agro-residues. Results In the present study, A. tubingensis FDHN1 was used for the xylanase, with very low level of cellulase, production under solid-state fermentation (SSF). Among various agro-residues, sorghum straw enhanced the xylanase production. Under optimized upstream conditions, the highest xylanase production 2,449 ± 23 U/g was observed. Upon characterization, crude xylanase showed stability over a broad range of pH 3.0 to 8.0 up to 24 h. The temperature stability revealed the nature of the xylanase to be thermostable. Native polyacrylamide gel electrophoresis (native PAGE) and zymogram analysis revealed the multiple forms of the xylanase. Due to the many industrially important characteristics of the xylanases, the study was elaborated for optimizing the downstream process parameters such as volume of extractant, extraction time, temperature and agitation speed to recover maximum xylanase from fermented sorghum straw. The highest amount of xylanase (4,105 ± 22 U/g) was recovered using 0.05 M sodium citrate buffer (pH 6.5) at 12:1 (v/w) extractant/solid ratio, 90-min extraction time, 150-rpm agitation speed and 40°C. Finally, detailed bioprocess optimization shows an overall 6.66-fold enhancement in the xylanase yield. Conclusions The present study consolidates the importance of upstream and downstream process optimization for the overall enhancement in the xylanase production. The xylanase from A. tubingensis FDHN1 shows the stability at different pH and temperature, and it was also active in the presence of organic solvents. These properties of xylanase are very much important from an industrial application point of view.

Hot-melt co-extrusion: requirements, challenges and opportunities for pharmaceutical applications

Co-extrusion implies the simultaneous hot-melt extrusion of two or more materials through the same die, creating a multi-layered extrudate. It is an innovative continuous production technology that offers numerous advantages over traditional pharmaceutical processing techniques. This review provides an overview of the co-extrusion equipment, material requirements and medical and pharmaceutical applications. The co-extrusion equipment needed for pharmaceutical production has been summarized. Because the geometrical design of the die dictates the shape of the final product, different die types have been discussed. As one of the major challenges at the moment is shaping the final product in a continuous way, an overview of downstream solutions for processing co-extrudates into drug products is provided. Layer adhesion, extrusion temperature and viscosity matching are pointed out as most important requirements for material selection. Examples of medical and pharmaceutical applications are presented and some recent findings considering the production of oral drug delivery systems have been summarized. Co-extrusion provides great potential for the continuous production of fixed-dose combination products which are gaining importance in pharmaceutical industry. There are still some barriers to the implementation of co-extrusion in the pharmaceutical industry. The optimization of downstream processing remains a point of attention.

Downstream processing of cell culture-derived virus particles

Manufacturing of cell culture-derived virus particles for vaccination and gene therapy is a rapidly growing field in the biopharmaceutical industry. The process involves a number of complex tasks and unit operations ranging from selection of host cells and virus strains for the cultivation in bioreactors to the purification and formulation of the final product. For the majority of cell culture-derived products, efforts focused on maximization of bioreactor yields, whereas design and optimization of downstream processes were often neglected. Owing to this biased focus, downstream procedures today often constitute a bottleneck in various manufacturing processes and account for the majority of the overall production costs. For efficient production methods, particularly in sight of constantly increasing economic pressure within human healthcare systems, highly productive downstream schemes have to be developed. Here, we discuss unit operations and downstream trains to purify virus particles for use as vaccines and vectors for gene therapy.

Application of statistical experimental design for optimization of downstream process for recovery of pullulan produced by Aureobasidium pullulans HP-2001

The optimal conditions of the downstream process for recovery of pullulan produced by Aureobasidium pullulans HP-2001 were examined using response surface method (RSM). The optimal amount of diatomite in filter press and the optimal flow rate in a continuous flow centrifuge for removal of cells from the culture broth of A. pullulans HP-2001 were found to be 5.0% (v/v) and 2.0 L/min. Based on central composite design (CCD) experiments and analysis of variance (ANOVA) indicated that the optimal conditions for recovery of pullulan from the supernatant by precipitation were the volume ratio of ethanol (or isopropanol) to supernatant of 3.0: 1.0, the reaction time of 29.5 h, and the reaction temperature of 20.2 °C. The expected maximal recovery yields of pullulan using ethanol and isopropanol under optimized conditions were 79.2 and 85.5%, respectively.

Two-stage, self-cycling process for the production of bacteriophages

BackgroundA two-stage, self-cycling process for the production of bacteriophages was developed. The first stage, containing only the uninfected host bacterium, was operated under self-cycling fermentation (SCF) conditions. This automated method, using the derivative of the carbon dioxide evolution rate (CER) as the control parameter, led to the synchronization of the host bacterium. The second stage, containing both the host and the phage, was operated using self-cycling infection (SCI) with CER and CER-derived data as the control parameters. When each infection cycle was terminated, phages were harvested and a new infection cycle was initiated by adding host cells from the SCF (first stage). This was augmented with fresh medium and the small amount of phages left from the previous cycle initiated the next infection cycle. Both stages were operated independently, except for this short period of time when the SCF harvest was added to the SCI to initiate the next cycle.ResultsIt was demonstrated that this mode of operation resulted in stable infection cycles if the growth of the host cells in the SCF was synchronized. The final phage titers obtained were reproducible among cycles and were as good as those obtained in batch productions performed under the same conditions (medium, temperature, initial multiplicity of infection, etc.). Moreover, phages obtained in different cycles showed no important difference in infectivity. Finally, it was shown that cell synchronization of the host cells in the first stage (SCF) not only maintained the volumetric productivity (phages per volume) but also led to higher specific productivity (phage per cell per hour) in the second stage (SCI).ConclusionsProduction of bacteriophage T4 in the semi-continuous, automated SCF/SCI system was efficient and reproducible from cycle to cycle. Synchronization of the host in the first stage prior to infection led to improvements in the specific productivity of phages in the second stage while maintaining the volumetric productivity. These results demonstrate the significant potential of this approach for both upstream and downstream process optimization.

Concentration of recombinant baculovirus by cation-exchange chromatography.

BioTechniquesVol. 26, No. 5 BenchmarksOpen AccessConcentration of Recombinant Baculovirus by Cation-Exchange ChromatographyJames BarsoumJames Barsoum*Address correspondence to Dr. James Barsoum, Biogen, Inc., 12 Cambridge Center, Cambridge, MA 02142, USA. Internet: E-mail Address: jim_barsoum@biogen.comBiogen, Cambridge, MA, USASearch for more papers by this authorPublished Online:22 Aug 2018https://doi.org/10.2144/99265bm07AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail FiguresReferencesRelatedDetailsCited ByProduction of Baculovirus and Stem Cells for Baculovirus-Mediated Gene Transfer into Human Mesenchymal Stem Cells22 September 2020Gene Expression in Mammalian Cells Using BacMam, a Modified Baculovirus SystemExpression and purification of recombinant feline interferon in the baculovirus-insect larvae systemProcess Biochemistry, Vol. 49, No. 6Virus Separation Using Membranes20 November 2013Membrane Supported Virus Separation from Biological Solutions14 June 2013 | Chemie Ingenieur Technik, Vol. 85, No. 8Purification of a recombinant baculovirus of Autographa californica M nucleopolyhedrovirus by ion exchange membrane chromatographyJournal of Virological Methods, Vol. 183, No. 2Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: Current advancesBiotechnology Advances, Vol. 29, No. 6Nonintegrating DNA Virus25 October 2011Baculovirus as vectors for human cells and applications in organ transplantationJournal of Invertebrate Pathology, Vol. 107Quality control and analytical methods for baculovirus-based productsJournal of Invertebrate Pathology, Vol. 107Requirements for baculoviruses for clinical gene therapy applicationsJournal of Invertebrate Pathology, Vol. 107Development and validation of a HPLC method for the quantification of baculovirus particlesJournal of Chromatography B, Vol. 879, No. 1High-titer preparation of Bombyx mori nucleopolyhedrovirus (BmNPV) displaying recombinant protein in silkworm larvae by size exclusion chromatography and its characterization12 June 2009 | BMC Biotechnology, Vol. 9, No. 1Enhancing the multiplication of nucleopolyhedrovirus in vitro by manipulation of the pHJournal of Virological Methods, Vol. 161, No. 2Purification of recombinant baculoviruses for gene therapy using membrane processes2 April 2009 | Gene Therapy, Vol. 16, No. 6Concanavalin a affinity chromatography for efficient baculovirus purificationBiotechnology Progress, Vol. 23Virus Production for Clinical Gene Therapy24 February 2009Targeting and Purification of Metabolically Biotinylated BaculovirusHuman Gene Therapy, Vol. 19, No. 6Baculovirus-Infected Insect Cells Expressing Peptide-MHC Complexes Elicit Protective Antitumor Immunity20 December 2007 | The Journal of Immunology, Vol. 180, No. 1Baculovirus envelope fusion proteins F and GP64 exploit distinct receptors to gain entry into cultured insect cellsJournal of General Virology, Vol. 88, No. 12Ion-Exchange Membrane Chromatography Method for Rapid and Efficient Purification of Recombinant Baculovirus and Baculovirus gp64 ProteinHuman Gene Therapy, Vol. 18, No. 7High yield purification of functional baculovirus vectors by size exclusion chromatographyJournal of Virological Methods, Vol. 142, No. 1-2Sampling Viruses from Soil14 May 2007Gene Expression in Mammalian Cells Using BacMam, a Modified Baculovirus SystemBaculovirus Vectors for Gene TherapyBaculovirus as a highly efficient expression vector in insect and mammalian cellsActa Pharmacologica Sinica, Vol. 26, No. 4Highly efficient baculovirus-mediated gene transfer into rat chondrocytes1 January 2004 | Biotechnology and Bioengineering, Vol. 88, No. 5Generation of chimeric baculovirus with histidine-tags displayed on the envelope and its purification using immobilized metal affinity chromatographyEnzyme and Microbial Technology, Vol. 33, No. 4Baculovirus as Mammalian Cell Expression Vector for Gene Therapy: An Emerging StrategyMolecular Therapy, Vol. 6, No. 1A novel system for the production of fully deleted adenovirus vectors that does not require helper adenovirus22 June 2001 | Gene Therapy, Vol. 8, No. 11Estimation of Baculovirus Titer by β-Galactosidase Activity Assay of Virus PreparationsTetsuro Yahata, Stephanie Andriole, Kurt J. Isselbacher & Toshi Shioda29 August 2018 | BioTechniques, Vol. 29, No. 2Application of Recombinant Baculoviruses in Biopharmaceutical Research Vol. 26, No. 5 Follow us on social media for the latest updates Metrics Downloaded 370 times History Published online 22 August 2018 Published in print May 1999 Information© 2018 Author(s)PDF download

Phase Partitioning of Biomolecules: Solubilities of Amino Acids

AbstractThe representation of phase equilibrium for amino acids, peptides, and proteins in solution is an important problem in the design and optimization of downstream processes for recovery of the biomolecules. This paper presents a molecular thermodynamic framework [1, 2] for the representation of the solubilities of amino acids and small peptides. With this framework, satisfactory results have been obtained in representing and predicting the solubilities of amino acids and small peptides in aqueous solution as functions of temperature, ionic strength, dipolar species concentrations, solvent compositions, and pH.