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Acetic acid stress represents a frequent challenge to counteract for yeast cells under several environmental conditions and industrial bioprocesses. The molecular mechanisms underlying its response have been mostly elucidated in the budding yeast Saccharomyces cerevisiae, where acetic acid can be either a physiological substrate or a stressor. This review will focus on acetic acid stress and its response in the context of cellular transport, pH homeostasis, metabolism and stress‐signalling pathways. This information has been integrated with the results obtained by multi‐omics, synthetic biology and metabolic engineering approaches aimed to identify major cellular players involved in acetic acid tolerance. In the production of biofuels and renewable chemicals from lignocellulosic biomass, the improvement of acetic acid tolerance is a key factor. In this view, how this knowledge could be used to contribute to the development and competitiveness of yeast cell factories for sustainable applications will be also discussed., Take Away Acetic acid stress is a frequent challenge for budding yeast.Signalling pathways dissection and system‐wide approaches reveal a complex picture.Cell fitness and adaptation under acid stress conditions is environment dependent.Tolerance to acetic acid is a key factor in yeast‐based industrial biotechnology.There is no ‘magic bullet’: An integrated approach is advantageous to develop performing yeast cell factories., Multiple factors influenced acetic acid stress and tolerance in the budding yeast Saccharomyces cerevisiae.

The power of microorganisms in manipulating diverse matrices and in favouring the flux of elements and molecules through biogeochemical cycles developed in the natural environment, but they also managed to take advantage of some niches created by humans. Therefore, inspired by learning these lessons from nature, we can implement biobased processes at industrial level, for diminishing our dependency on fossil resources and to return molecules to their turnover in a compatible timeframe and with reduced environmental impact.

Microbial cell factories are the workhorses of industrial biotechnology and improving their performances can significantly optimize industrial bioprocesses. Microbial strain engineering is often employed for increasing the competitiveness of bio‐based product synthesis over more classical petroleum‐based synthesis. Recently, efforts for strain optimization have been standardized within the iterative concept of “design‐build‐test‐learn” (DBTL). This approach has been successfully employed for the improvement of traditional cell factories like Escherichia coli and Saccharomyces cerevisiae. Within the past decade, several new‐to‐industry microorganisms have been investigated as novel cell factories, including the versatile α‐proteobacterium Rhodobacter sphaeroides. Despite its history as a laboratory strain for fundamental studies, there is a growing interest in this bacterium for its ability to synthesize relevant compounds for the bioeconomy, such as isoprenoids, poly‐β‐hydroxybutyrate, and hydrogen. In this study, we reflect on the reasons for establishing R. sphaeroides as a cell factory from the perspective of the DBTL concept. Moreover, we discuss current and future opportunities for extending the use of this microorganism for the bio‐based economy. We believe that applying the DBTL pipeline for R. sphaeroides will further strengthen its relevance as a microbial cell factory. Moreover, the proposed use of strain engineering via the DBTL approach may be extended to other microorganisms that have not been critically investigated yet for industrial applications., Rhodobacter sphaeroides is a purple non‐sulfur bacteria which has served for decades as model laboratory strain for fundamental studies. Nevertheless, in the last decades this microorganism has matured into a versatile microbial cell factory for multiple biotechnological processes. In this work, authors describe this transition by means of the ‘design‐build‐test‐learn’ concept for strain engineering.

Filamentous fungi are widely used in the production of biotechnological compounds. Since their morphology is strongly linked to productivity, it is a key parameter in industrial biotechnology. However, identifying the morphological properties of filamentous fungi is challenging. Owing to a lack of appropriate methods, the detailed three-dimensional morphology of filamentous pellets remains unexplored. In the present study, we used state-of-the-art X-ray microtomography (µCT) to develop a new method for detailed characterization of fungal pellets. µCT measurements were performed using freeze-dried pellets obtained from submerged cultivations. Three-dimensional images were generated and analyzed to locate and quantify hyphal material, tips, and branches. As a result, morphological properties including hyphal length, tip number, branch number, hyphal growth unit, porosity, and hyphal average diameter were ascertained. To validate the potential of the new method, two fungal pellets were studied-one from Aspergillus niger and the other from Penicillium chrysogenum. We show here that µCT analysis is a promising tool to study the three-dimensional structure of pellet-forming filamentous microorganisms in utmost detail. The knowledge gained can be used to understand and thus optimize pellet structures by means of appropriate process or genetic control in biotechnological applications.

To realize the potential of microalgae in the biorefinery context, exploitation of multiple products is necessary for profitability and bioproduct valorization. Appropriate analytical tools are required for growth optimization, culture monitoring, and quality control purposes, with safe, low‐tech, and low‐cost solutions favorable. Rapid, high‐throughput, and user‐friendly methodologies were devised for (a) determination of phycobiliproteins, chlorophylls, carotenoids, proteins, carbohydrates, and lipids and (b) qualitative and quantitative carotenoid profiling using UPLC‐PDA‐MSE. The complementary methods were applied on 11 commercially important microalgal strains including prasinophytes, haptophytes, and cyanobacteria, highlighting the suitability of some strains for coproduct exploitation and the method utility for research and industrial biotechnology applications. The UPLC method allowed separation of 41 different carotenoid compounds in, Rapid, user‐friendly methodologies were devised for the determination of phycobiliprotein, pigment, and macromolecule contents in microalgae, and for qualitative and quantitative carotenoid profiling using liquid chromatography coupled with spectrophotometry and mass spectrometry. Methods were applied to commercially important microalgal strains, demonstrating their application and suitability as tools for quality control, strain selection, and growth optimization purposes within microalgal research and integrated biorefinery settings.

Sustainable production of biofuels and other valuable compounds is one of our future challenges. One tempting possibility is to use photosynthetic cyanobacteria as production factories. Currently, tools for genetic engineering of cyanobacteria are not good enough to exploit the full potential of cyanobacteria. A wide variety of expression systems will be required to adjust both the expression of heterologous enzyme(s) and metabolic routes to the best possible balance, allowing the optimal production of a particular substance. In bacteria, transcription, especially the initiation of transcription, has a central role in adjusting gene expression and thus also metabolic fluxes of cells according to environmental cues. Here we summarize the recent progress in developing tools for efficient cyanofactories, focusing especially on transcriptional regulation.

Microbial fermentation of renewable feedstocks is an established technology in industrial biotechnology. Besides strict aerobic or anaerobic modes of operation, novel innovative and industrially applicable fermentation processes were developed connecting the advantages of aerobic and anaerobic conditions in a combined production approach. As a consequence, rapid aerobic biomass formation to high cell densities and subsequent anaerobic high‐yield and zero‐growth production is realized. Following this strategy, bioprocesses operating with substantial overall yield and productivity can be obtained. Here, we summarize the current knowledge and achievements in such microbial zero‐growth production processes and pinpoint to challenges due to the complex adaptation of the cellular metabolism during the cell's passage from aerobiosis to anaerobiosis.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. To realize the potential of human embryonic stem cells (hESCs) in regenerative medicine and drug discovery applications, large numbers of cells that accurately recapitulate cell and tissue function must be robustly produced. Previous studies have suggested that genetic instability and epigenetic changes occur as a consequence of enzymatic passaging. However, the potential impacts of such passaging methods on the metabolism of hESCs have not been described. Using stable isotope tracing and mass spectrometry-based metabolomics, we have explored how different passaging reagents impact hESC metabolism. Enzymatic passaging caused significant decreases in glucose utilization throughout central carbon metabolism along with attenuated de novo lipogenesis. In addition, we developed and validated a method for rapidly quantifying glycan abundance and isotopic labeling in hydrolyzed biomass. Enzymatic passaging reagents significantly altered levels of glycans immediately after digestion but surprisingly glucose contribution to glycans was not affected. These results demonstrate that there is an immediate effect on hESC metabolism after enzymatic passaging in both central carbon metabolism and biosynthesis. HESCs subjected to enzymatic passaging are routinely placed in a state requiring re-synthesis of biomass components, subtly influencing their metabolic needs in a manner that may impact cell performance in regenerative medicine applications. Stable isotope tracing and targeted metabolomics identifies specific, deleterious impacts of enzyme-based passaging methods on the metabolic behavior of human embryonic stem cells (hESCs). Enzymatic passaging of hESCs decreases glucose catabolism, fatty acid synthesis, and glycan abundance. These results provide insights into potential selective pressures placed on hESCs during expansion and subculture.

After finishing high school in Pinsk, Russia, Chaim Weizmann studied two semesters in the Technical University of Darmstadt, returned home for a year, and in 1895 registered as a chemistry student at the Charlottenburg Technical University at Berlin. He studied and worked in the research group of A. Bistrzycki on synthetic dyestuffs and received a patent in the field. He graduated after 3 years and followed Bistrzycki to Freiburg, Switzerland, where he received in January 1899 a Ph.D. degree with a grade of Magna cum laude. He became a Privatdocent at the University of Geneva, worked in Prof. C. Graebe’s group, published papers and patents and sold patents. In 1904, he moved to the University of Manchester in the UK and collaborated with Prof. William Henry Perkin Jr. in research on synthetic dyestuffs and natural products, and started to work with him on the synthesis of acetone by fermentation. He failed to be nominated to Perkin’s chair when Perkin left in 1913, but became a Reader and head of the biochemistry laboratory. After a conflict with Perkin, he continued alone with the acetone synthesis project, found a bacterium that fermented the starch of corn, potatoes, and chestnuts to acetone and butyl alcohol, which was more efficient than a bacterium found by Perkin and co-workers. The urgent need for acetone in World War One for military purpose and the high yield of his bacterium in acetone-producing fermentation, compared with the bacterium of his competitors, made Weizmann’s process the favored one by the British military during the war. Weizmann scaled up acetone production and increased its yield by increasing the sophistication of the process by using a high degree of sterilization. For his contributions he is regarded as the father of industrial biotechnology. His contribution to the war effort opened the door to the British leadership in his Zionistic activity. However, this activity and his scientific activity at later periods are not covered in this article.

The Center of Industrial Biotechnology (CIBT) was established in Huzhou for fine chemicals in 2006 and CIBT Shanghai was founded for bulk chemicals in 2008. CIBT is a non-profit organization under auspices of the Shanghai Institutes for Biological Sciences, Shanghai Branch of the Chinese Academy of Sciences (CAS) and Huzhou Municipal Government. CIBT is affiliated with the CAS, which enables it to take advantage of the rich RD resources and support from CAS; yet CIBT operates as an independent legal entity. The goal of CIBT is to incubate industrial biotechnologies and accelerate the commercialization of these technologies with corporate partners in China.

Natural products are always in demand, especially in the food and water treatment industry, to reduce health hazards caused by the prolonged use of chemicals. Though crude seed extract of Moringa o ...

The discriminatory power of the noncoding control region (CR) of domestic dog mitochondrial DNA alone is relatively low. The extent to which the discriminatory power could be increased by analyzing additional highly variable coding regions of the mitochondrial genome (mtGenome) was therefore investigated. Genetic variability across the mtGenome was evaluated by phylogenetic analysis, and the three most variable ~1 kb coding regions identified. We then sampled 100 Swedish dogs to represent breeds in accordance with their frequency in the Swedish population. A previously published dataset of 59 dog mtGenomes collected in the United States was also analyzed. Inclusion of the three coding regions increased the exclusion capacity considerably for the Swedish sample, from 0.920 for the CR alone to 0.964 for all four regions. The number of mtDNA types among all 159 dogs increased from 41 to 72, the four most frequent CR haplotypes being resolved into 22 different haplotypes.

The chemical industry has made a contribution to modern society by providing cost-competitive products for our daily use. However, it now faces a serious challenge regarding environmental pollutions and greenhouse gas emission. With the rapid development of molecular biology, biochemistry, and synthetic biology, industrial biotechnology has evolved to become more efficient for production of chemicals and materials. However, in contrast to chemical industries, current industrial biotechnology (CIB) is still not competitive for production of chemicals, materials, and biofuels due to their low efficiency and complicated sterilization processes as well as high-energy consumption. It must be further developed into "next-generation industrial biotechnology" (NGIB), which is low-cost mixed substrates based on less freshwater consumption, energy-saving, and long-lasting open continuous intelligent processing, overcoming the shortcomings of CIB and transforming the CIB into competitive processes. Contamination-resistant microorganism as chassis is the key to a successful NGIB, which requires resistance to microbial or phage contaminations, and available tools and methods for metabolic or synthetic biology engineering. This review proposes a list of contamination-resistant bacteria and takes Halomonas spp. as an example for the production of a variety of products, including polyhydroxyalkanoates under open- and continuous-processing conditions proposed for NGIB.

Bacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine. This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized. We have also discussed approved phage-based products (whole phage-based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations. Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.

The efficiency of the protein refolding process lies in identification of the optimal conditions. However, a number of challenges need to be overcome to achieve this. This review first describes the protein refolding process that is utilized presently for production of protein therapeutics. Next, it discusses the various shortcomings that exist with respect to the present approach. The focus of the paper is on presentation of the significant advancements that have been made in the past decade in the various aspects of protein folding, including use of bioinformatics, mechanistic modeling, analytical monitoring, process optimization, use of additives, high throughput development, on-column refolding, Quality by Design (QbD), Process Analytical Technology (PAT), and process intensification. Finally, an approach is proposed that incorporates the best practices that have been identified in the various areas. The paper is expected to be of interest to those in academia and industry working in the area of protein refolding. © 2013 Society of Chemical Industry.

Within the last decade, biotechnology gained pace in substituting petro-based products for the chemical industries. This is visible with the appearance of bio-based products in the market, from biosurfactants to bio-based polymers like polylactic acid to bio-ethylene. These technologies are mainly based on established fermentation technologies fostered by the use of renewable resources, culminating in the establishment of biorefineries that may be connected directly to the existing chemical infrastructure. Besides these large-scale technologies, the combination of molecular technologies, microfluidic devices, and enzymatic and cell-free conversions are currently developed to create new bioproduction systems enabling the production of compounds that may not be produced within a cell. This article summarizes some of the current ideas that are currently in development paving the way for a next generation of biotechnology.

Die tropfchenbasierte Mikrofluidik dient der Isolierung und Manipulation von einzelnen Zellen und Reagentien innerhalb von monodispersen, pikolitergrosen Flussigkapseln bei einem Umsatz von tausenden Tropfchen pro Sekunde. Diese Qualitaten machen die Tropfchen-Mikrofluidik geeignet fur viele Anforderungen der Einzelzellanalyse. Durch die Monodispersitat lasst sich die Konzentration in den Tropfchen quantitativ einstellen. Die Tropfchen bieten der Zelle und ihrer unmittelbaren Umgebung ein isoliertes Kompartiment, und bei einem Durchsatz von tausenden Tropfchen pro Sekunde ist es moglich, zehntausende bis millionen verkapselte Zellen zu prozessieren. Heterogene Zellpopulationen lassen sich somit exakt beschreiben oder seltene Zellarten identifizieren. Das kleine Volumen der Tropfchen macht auch sehr grose Screenings okonomisch machbar. Dieser Aufsatz gibt einen Uberblick uber den aktuellen Stand der Einzelzellanalyse durch die Tropfchen-Mikrofluidik und nennt Beispiele, bei denen sie biologische Vorgange besser verstehen hilft.

The connection between production of energy and climate change is elucidated. CO2 from burning fossil carbon is the main agent responsible for the hazardous climatic development. The use of this process in energy production has to be vigorously restricted. The gaps have to be filled by conversion of renewable carbon into reduced forms. Big industry shall adopt biotechnology as an enabling technology.

BACKGROUND: The fire ant, Solenopsis invicta, is one of the most aggressive and invasive species in the world. The trail pheromoneZ,E-α-farnesene(91%purity)wasprepared,anddisruptionofworkertrailorientationwastestedusinganethanolbasedaerosolformulationpresentingasinglepuffofthiscompoundbyairbrushandcompressedair.Trail-followingbehaviour was recorded by overhead webcam and ants digitised before and after presentation of the aerosol treatment at four rates (1.6, 16, 160 and 1600 ng cm −2 ). RESULTS: Ants preferred 110 ng cm −1 over 11, 1.1 and 0.11 ng cm −1 for trail following. Within seconds of presentation of 1600 ng cm −2 , the highest dose tested, trail disruption was observed. Disruption was evident as reduced arrival success and reduction in the trail integrity statistic (r 2 ), as well as increased deviation from the trail (deg). The distribution of walking track angles was also flattened. CONCLUSIONS: The feasibility of using aerosol for delivery of trail pheromone was demonstrated, but the need for high purity combined with the difficulty of commercial supply makes this technique impractical. However, the commercial production of Z,E-α-farnesene of high purity by industrial biotechnology or from (E)-nerolidol may be possible in future, which would facilitate further development of trail pheromone disruption ofS.invicta. c � 2012 Society of Chemical Industry

Cryostructuration platform renders it possible to form macroporous materials (known as cryogels) with a broad range of porosity, from structures with combination of meso- and macropores to structures with 100-μm sized macropores. When these materials are formed in the shape of monoliths (monolithic cryogels), they present a unique monolithic stationary medium for specific applications. This review summarizes the recent research on the preparation and characterization of cryostructurated monolithic cryogels for (bio)separation and points to some future perspectives.

Constant progress in genetic engineering has given rise to a number of promising areas of research that facilitated the expansion of industrial biotechnology. The field of metabolic engineering, which utilizes genetic tools to manipulate microbial metabolism to enhance the production of compounds of interest, has had a particularly strong impact by providing new platforms for chemical production. Recent developments in synthetic biology promise to expand the metabolic engineering toolbox further by creating novel biological components for pathway design. The present review addresses some of the recent advances in synthetic biology and how these have the potential to affect metabolic engineering in the yeast Saccharomyces cerevisiae. While S. cerevisiae for years has been a robust industrial organism and the target of multiple metabolic engineering trials, its potential for synthetic biology has remained relatively unexplored and further research in this field could strongly contribute to industrial biotechnology. This review also addresses are general considerations for pathway design, ranging from individual components to regulatory systems, overall pathway considerations and whole-organism engineering, with an emphasis on potential contributions of synthetic biology to these areas. Some examples of applications for yeast synthetic biology and metabolic engineering are also discussed.

The effects of ionic substances in seven industrial filtrates from kraft pulping, mechanical pulping, and sulfite pulping on the activity of oxalate oxidase from barley were investigated by pre-tre ...

The development of industrial biotechnology for an economical and ecological conversion of renewable materials into chemicals and fuels requires new strategies and concepts for bioprocessing. Biorefinery has been proposed as one of the key concepts with the aim of completely utilizing the substrate(s) and producing multiple products in one process or at one production site. In this article, we argue that microbial consortia can play an essential role to this end. To illustrate this, we first briefly describe some examples of existing industrial bioprocesses involving microbial consortia. New bioprocesses under development which make use of the advantages of microbial consortia are then introduced. Finally, we address some of the key issues and challenges for the analysis and engineering of bioprocesses involving microbial consortia from a perspective of biosystems engineering.

Developing methylotrophic bacteria into cell factories that meet the chemical demand of the future could be both economical and environmentally friendly. Methane is not only an abundant, low‐cost resource but also a potent greenhouse gas, the capture of which could help to reduce greenhouse gas emissions. Rational strain design workflows rely on the availability of carefully combined knowledge often in the form of genome‐scale metabolic models to construct high‐producer organisms. In this review, the authors present the most recent genome‐scale metabolic models in aerobic methylotrophy and their applications. Further, the authors present models for the study of anaerobic methanotrophy through reverse methanogenesis and suggest organisms that may be of interest for expanding one‐carbon industrial biotechnology. Metabolic models of methylotrophs are scarce, yet they are important first steps toward rational strain‐design in these organisms.

Das von Theodor Escherich vor 125 Jahren entdeckte E. coli-Bakterium hat wie kein anderes die Entwicklung der molekularbiologischen Forschung und der medizinischen und industriellen Biotechnologie beeinflusst. Vor allem die Eigenschaften des K12-Stammes im Hinblick auf Apathogenitat, Kultivierbarkeit und Transformierbarkeit haben E. coli zum “Haustier” der Genetiker und Molekularbiologen gemacht. Die Leichtigkeit, mit der gentechnisch veranderte E. coli hergestellt werden konnen, liesen dieses Bakterium zum beliebten Produktionsorganismus in der modernen Biotechnologie zur Erzeugung von Medikamenten und Feinchemikalien werden. Als physiologischer Darmbewohner von Menschen und Tieren wird E. coli als Indikatororganismus fur fakale Verunreinigungen von Grund- und Trinkwasser verwendet. Neben seiner mikrookologischen Rolle im Magen-Darm-Trakt kommt ihm in Form von pathogenen Stammen auch eine Bedeutung als Erreger von Durchfallerkrankungen zu. The history of colibacteria The E. coli bacterium discovered by Theodor Escherich 125 years ago has influenced the development of molecular-biological research and medicinal and industrial biotechnology like no other bacterium. In particular, the characteristics of the K12-strain with respect to apathogenicity, culturability and transformability made E. coli the “workhorse” of geneticists and molecular biologists. The easiness with which genetically modified E. coli can be made let this bacterium become a popular production organism of modern biotechnology for the making of drugs and fine chemicals. As a physiological inhabitant of the intestine of humans and animals, E. coli is used as an indicator organism of faecal pollution of ground and drinking water. Alongside its micro-ecological role in the gastrointestinal tract, the E. coli bacterium, in terms of pathogenic strains, also has significance as a causative agent of diarrhoeal diseases.

High-abundant plasma proteins pose a challenge in a large number of proteomics-based technologies. Depletion of these high-abundant proteins has proven to be a fruitful strategy to circumvent masking of lower-abundant proteins that could serve as valuable biomarker candidates. However, current strategies often do not meet the throughput requirements of large-scale proteomic studies. In the present paper, a flexible and parallelized method for the depletion of high-abundant proteins is described, allowing the removal of the two most abundant proteins from 48 blood-derived samples in less than 15 min using Affibody molecules as affinity ligands. A sample-processing platform like this should be suitable for a number of proteomics technologies; its flexibility in buffer composition allows for different types of downstream applications.

Thanks to its ease of use, modularity, and scalability, the clustered regularly interspaced short palindromic repeats (CRISPR) system has been increasingly used in the design and engineering of Saccharomyces cerevisiae, one of the most popular hosts for industrial biotechnology. This review summarizes the recent development of this disruptive technology for metabolic engineering applications, including CRISPR-mediated gene knock-out and knock-in as well as transcriptional activation and interference. More importantly, multi-functional CRISPR systems that combine both gain- and loss-of-function modulations for combinatorial metabolic engineering are highlighted.