BiotecVisions 2013, August

Focus: Industrial Biotechnology

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Editors: Judy Peng /jp; Lucie Kalvodova /lk


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Contributors: Frances Harding /fh; Meghana Hemphill /mh; Owain Jevons /oj; Mia Ricci /mr; Frédérique Belliard /fb; Erwin Ripmeester /er; Gillian van Beest /gvb; Danny Asling /ds; Allison Goldenstein /ag; Anja Stephan /as; Karin Tiemann /kt

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August 2013


Advanced Analytics for Therapeutic Proteins: from Research to Manufacturing

Where: Kloster Irsee, Germany

When: 18–20 September, 2013

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Development and manufacturing of biopharmaceuticals require highly sophisticated analytics at all stages of the process. These drug development programs are currently facing a higher attrition rate and an increasing regulatory demand to characterize the product and manufacturing process. More recently, the emerging portfolio of biosimilar programs is driving another leap in understanding how the manufacturing process defines product quality.

The conference “Advanced Analytics for Therapeutic Proteins: from Research to Manufacturing” aims to bring researchers from academia and industry together to discuss novel trends in analytical science. It will focus on all approaches that aim to lower attrition, improve characterization of products and impurities and increase process knowledge and safety.

International leaders in the field will present today's technology and an outlook on the future. Nine keynote addresses are highlights of the lecture program.

The Scientific Committee cordially invites you to this event and looks forward to meeting colleagues and old friends, introducing newcomers to the area of analytical science in biopharma, and experiencing lively interactions and discussions on the newest hot topics of the field. /kt

Getting published

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Discoverability of your article

As mentioned in our previous article in this column on the H-index, discoverability is crucial to the eventual citation of your research results. There are many aspects to discoverability, starting with the title of the paper and this column has covered many aspects of writing a scientific paper. This time, we will discuss how to use the latest digital technologies to help disseminate your research to a wider audience.

It used to be that once a paper is accepted and the authors have approved the final galley proofs, the work of the authors is done. These days, with social media and digital technology changing many of the ways we used to do things, there is much more that you, as an author, are able to do in promoting your research. Some suggestions include:

PDF sharing: many publishers allow authors to share the final PDFS with their colleagues and friends – make use of this opportunity if it is available.

Open Access: many traditional journals also have the option of publishing articles as “Open Access” articles. This of course allows access to your research by all who are interested; it may be a worthwhile option to further promote availability of your articles.

Link to your article: the internet is about connectivity and articles that are well linked are also ranked higher in search engine results. In you have an institutional homepage where you list your publications, be sure that the articles are hyperlinked (via the title of the article), to the webpage where the official article is hosted. This greatly improves the search engine rankings of your article.

Social media: tell your friends and colleagues via Facebook, Twitter, LinkedIn, etc. that your paper is now online, providing the link to the article. Another new way of promoting your article is to post a short video on your research on channels such as YouTube and linking this to your article. /jp

What is the H-index

Cover story

Cell-free conversion concepts for industrial biotechnology

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Fermentation processes are the original biotechnology tracing back to the brewing of beer-like beverages already in ancient times. Recently, technologies to expand the genetic code of microorganisms have been developed to open a completely new avenue of chemistry within cells and beyond. In addition, cell-free systems based on either ordered chains of enzymatic reactions or cell-free lysates from microorganisms allow the highly specific production of both proteins and metabolites without any physical barrier such as membranes. These novel concepts in biotechnology certainly have the potential to enrich industrial biotechnology in the near future by a wider product spectrum and novel bioprocess technologies. This review in Engineering in Life Sciences brings together several recent developments in biotechnology to describe a vision of the “next generation biotechnology”.

PHA: The plant polymers that keep on giving

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Large scale production of polyhydroxyalkanoates (PHAs) in plants can provide a sustainable supply of bioplastics, biochemicals, and energy from sunlight and atmospheric CO2. PHAs are a class of polymers with various chain lengths that are naturally produced by some microorganisms as storage materials. The properties of these polyesters make them functionally equivalent to many of the petroleum-based plastics that are currently in the market place. However, unlike most petroleum-derived plastics, PHAs can be produced from renewable feedstocks and easily degrade in most biologically active environments. This review from Plant Biotechnology Journal highlights research efforts over the last 20 years to engineer the production of PHAs in plants, with a focus on polyhydroxybutryrate (PHB) production in bioenergy crops with C4 photosynthesis. /oj

Integrated approach aids fermentation and downstream process development

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Fermentation parameters shape cell physiology, impacting the efficacy of downstream processing strategies. In recent work published in Biotechnology Progress, the influence of mild hypothermic conditions exerted during CHO cell fermentation on antibody recovery was assessed. Reducing fermentation temperature from 37°C to 32°C allowed the fermentation culture period to be extended, increasing the product titre at harvest. However, the same conditions had a mixed effect on downstream processing, raising the host cell protein load by 50% but improving the ease of product stream clarification. This work demonstrates the value of an integrated approach to mammalian bioprocess design across upstream and downstream operations. /fh

Rapid chromatography process development using high throughput screening

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Biotherapeutics must be formulated free of any contaminating virus. As an adjunct to pH activation and filtration, chromatographic steps are often included in purification bioprocesses to assist with virus removal. A feasibility study published in Biotechnology and Bioengineering examines the application of a high throughput screening strategy to define the operation space required for effective chromatographic virus removal. By incorporating robotic handling, a broad range of operating conditions could be assessed in full factorial combination within a short time frame and using limited material volumes. The plate based assay provided a good approximation of product and impurity partitioning occurring under equivalent conditions in the column format, allowing key operational parameters to be identified and basic sensitivity analyses to be performed. /fh

Robotized quantification of fatty acids by GLC

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Fatty acid profiling and quantification in fats and oils can be performed by analyzing their fatty acid methyl esters (FAME) using gas–liquid chromatography (GLC). GLC instruments equipped with online sample preparation units have recently become commercially available. Beggio, Destaillats et al. present a validated procedure for the quantitative analysis of fatty acids in fats and oils by robotic preparation and online GLC analysis of FAME that can be easily implemented in laboratories dealing with a large number of fats and oils samples every day. The procedure has good repeatability and good intermediate reproducibility, and compared to the manual procedure requires three times less reagent and solvent per sample. /lk

Fish by-products as a source of novel marine lipases for industrial applications

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Marine lipases have unique properties which can be used in specific applications including flavour development in dairy products, lipid hydrolysis and synthesis of specialty lipids such as omega-3 concentrates. Although microorganisms will continue to supply the majority of lipases for industrial applications, fish by-products provide an alternative source of novel lipases with the potential to be extracted economically at large scale.

Valuable biomolecules originate from microreactors

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As fossil-based resources become more scarce, chemicals from biomass offer an attractive option, albeit at a reduced efficiency. Thus novel process technologies for biomass valorization to improve the efficiency of the conversion processes are needed. Various naturally available carbohydrates and amino acids have been used lately as the starting material for synthesis of valuable key intermediates and pharmaceuticals. At the same time, microreaction technology is being developed and is seen as an effective way to intensify a process. Can microreaction technology be an enabling tool for commercial and cost-effective bio-based processes? Microreactors enable the reduction of consecutive reactions, simplification of the separation chain and optimization of reaction conditions; however, integration of chemistry and engineering disciplines is needed before undergoing a complex batch-to-flow process change. This review outlines the industrial potential of microreactors and addresses the issues of process integration and a holistic process design approach.

Understanding the metabolism of cyanobacteria with multi-omics analysis

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Cyanobacteria have received considerable attention as a sustainable energy resource because of their capacity to produce organic materials using CO2 as a carbon source, and energy from light. Therefore, understanding the metabolism of cyanobacteria is important for the area of cyanobacterial metabolic engineering. Multi-omics analysis is a powerful tool for understanding complex metabolisms; however, there are relatively few omics studies on cyanobacteria. Yoshikawa et al. (Osaka University, Japan) report transcriptomic and metabolomic analyses of Synechocystis sp. PCC 6803 under different trophic conditions, such as autotrophic, mixotrophic and photoheterotrophic conditions. The omics dataset reported in this work provides clues to help better understand the metabolism of cyanobacteria.

“Convincing” microbes to use synthetic pathways

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Synthetic metabolic pathways enable microbes to produce new biofuels and value-added commodity chemicals. However, metabolic engineers are faced with the challenge of ensuring that the engineered microbe continue to uses these synthetic pathways and that production remains high as the engineered strain evolves. Previous approaches have used computational modeling of metabolism to identify gene knockouts and up/down gene regulatory strategies to improve microbial productivity and guide evolution. Yen et al. (Virginia Tech, USA) introduce a new modeling strategy based on “flux ratios”. The new approach, called flux balance analysis using flux ratios (FBrAtio) enables identification of “fine-tuned” metabolic engineering strategies that lead to optimum product formation rates. The FBrAtio approach is tested by the authors on five separate case studies with publicly available genome-scale metabolic flux models, and is shown to successfully guide the development of effective metabolic engineering strategies.

Continuous flux modifications provide flexibility in strain design

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Strain design algorithms are used to facilitate metabolic engineering efforts by systematically identifying genetic changes that will cause an organism to increase production of a desired chemical. Existing constraint-based methods use a variety of techniques with some strengths and limitations. Cotten and Reed (University of Wisconsin-Madison, USA) report the development of a computational method (CosMos) that encompasses several previously reported techniques, while overcoming their limitations. CosMos considers continuous changes to fluxes rather than using pre-determined values as done previously. As a result, CosMos leads to novel strain designs that cannot be derived with current approaches.

A quantitative analysis of microalgal lipids for optimization of biodiesel and omega-3 production

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The design of optimized processes for converting algal biomass to biodiesel requires detailed understanding of the lipid content of different algal species and how this varies under different growth conditions. While many techniques are available for lipid analysis, most are not able to provide the quantitative information required for this purpose. In this recent Biotechnology and Bioengineering article, Gregory J. O. Martin and coworkers outline a method for a detailed characterization of microalgal lipids that is targeted towards optimization of biodiesel production.

Transcriptional profiling of Brazilian S. cerevisiae strains

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The authors present a genome-wide analysis of the CAT-1 and PE-2 transcriptomes during a small-scale fermentation process simulating the unique Brazilian industrial conditions. This study in FEMS Yeast Research shows the importance of environmental stress tolerance and the UPR for efficient fermentation and successful yeast cell proliferation, when the acid treatment and recycling of yeast cell are used. This investigation demonstrated the shared and novel transcriptional response of the two Brazilian strains to the unique Brazilian fermentation process. These genes represent an opportunity for the genetic enhancement of these naturally selected industrial strains./fb

Genetic engineering of Lactobacillus diolivorans

The authors report in the second July issue of FEMS Microbiology Letters their newly developed toolbox for genetic manipulation of Lactobacillus diolivorans, a promising production organism for 1,3-propanediol from glycerol. Functional expression of proteins, both homologously and heterologously, could be achieved via an expression plasmid, pSHM, which is based on the replication origin repA of L. diolivorans. /er

MAP codon optimisation

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This study in the June Issue of Pathogens and Disease demonstrates that codon optimization improves expression and hence provides a simple but effective way to increase expression levels of the target antigen in a host organism. The underlying approach of expressing Mycobacterium avium paratuberculosis (MAP) genes in Lactobacillus strains has the potential to help immunize cattle against Johne's disease. As the first direct assessment of the impact of MAP codon bias on expression in a heterologous host, this study is of importance to the field. The authors suggest that due to the continuously decreasing and relative low cost of gene synthesis codon optimisation should be considered for subsequent recombinant MAP-antigen applications. /gvb

The secretory pathway: exploring yeast diversity

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The ever growing demand of biopharmaceuticals and the need for large amounts of enzymes mainly in the upcoming biorefinery industry substantiate a huge demand for efficient protein production processes, which mostly rely on the secretion capacity of the production host. This article in FEMS Microbiology Reviews provides a current overview of the canonical protein secretion pathway in the model yeast Saccharomyces cerevisiae including a genomic comparison of the S. cerevisiae pathway to seven other yeast species where secretion has been investigated due to their attraction as protein production platforms, or for their relevance as pathogens. /gvb

Feed rate control in fed-batch fermentations based on frequency content analysis

In the May/June 2013 issue of Biotechnology Progress, Ola Johnsson and coworkers presented a new strategy for controlling substrate feed in the exponential growth phase of aerated fed-batch fermentations. The challenge in this phase is typically to maximize specific growth rate while avoiding the accumulation of overflow metabolites which can occur at high substrate feed rates. In the new strategy, regular perturbations to the feed rate are applied and the proximity to overflow metabolism is continuously assessed from the frequency spectrum of the dissolved oxygen signal. The power spectral density for the frequency of the external perturbations is used as a control variable in a controller to regulate the substrate feed. The strategy was implemented in an industrial pilot scale fermentation set up and calibrated and verified using an amylase producing Bacillus licheniformis strain. It was shown that a higher biomass yield could be obtained without excessive accumulation of harmful overflow metabolites. The general applicability of the strategy was further demonstrated by implementing the controller in another process using a Bacillus licheniformis strain currently used in industrial production processes. In addition, in this case a higher growth rate and decreased accumulation of overflow metabolites in the exponential growth phase was achieved in comparison to the reference controller.

Gram-scale chemical synthesis of 2'-deoxynucleoside-5'-O-triphosphates

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Gram-scale chemical synthesis of the sodium salt of 2'-deoxynucleoside-5'-O-triphosphates (dNTPs), starting from the corresponding nucleoside, is described in a simple, straightforward, reliable, and efficient procedure in Current Protocols in Nucleic Acid Chemistry. This improved “one-pot, three-step” synthetic strategy involves the monophosphorylation of nucleoside, followed by reaction with tributylammonium pyrophosphate and hydrolysis of the resulting cyclic intermediate to provide the corresponding dNTP in good yields (65% to 70%).


Call for Nominations: 2014 B&B Daniel I. C. Wang Award

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Please note that the call for nominations for the 2014 B&B D.I.C. Wang Award closes August 31, 2013. The B&B Daniel I.C. Wang Award was initiated in 2008 to honor a younger member of our dynamic community and is presented annually at the National ACS Meeting at a session of the BIOT. Information is available on the journal homepage at the link provided below.


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Metabolic engineering: Enabling technology for biofuels production

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Metabolic engineering is the systematic attempt to understand, design, and engineer cellular metabolic networks using a wide range of interdisciplinary tools and strategies. In this review from WIREs Energy and Environment, Tai and Stephanopoulos present several examples of current research demonstrating how metabolic engineering has begun to contribute both novel and creative solutions toward bringing promising biofuel technologies to fruition: production of higher chain alcohols, fermentation of lignocellulosic material, and production of fatty acid derivatives.

Fatty acid oxidation: systems analysis and applications

Recent advances in metabolic engineering and systems biology have powered the study of fatty acid (FA) biosynthetic and catabolic routes in microorganisms at a systems level. Several studies have proposed these pathways as platforms for the production of fuels and chemicals from biorenewable sources. In this review from WIREs Systems Biology and Medicine, Cintolesi et al. present a comparison of the three main FA oxidative routes, systems biology analyses that have been used to study FA metabolism, and engineering efforts performed on microbial systems.

IUBMB Events

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7th International Conference on Protein Kinase CK2

Where: Lublin, Poland

When: September 10–13, 2013

IUBMB Advanced School: Protein interactions, assemblies and human disease

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Where: Island of Spetses, Greece

When: September 16–26, 2013

8th General Meeting of the International Proteolysis Society

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Where: Cape Town, South Africa

When: October 20–24, 2013

14th IUBMB Conference

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Where: Marrakech, Morocco

When: November 16–20, 2013

Abstract submission: August 12, 2013

Early registration: August 12, 2013

AFOB Events

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Thai Society for Biotechnology International Forum 2013

Where: Bangkok, Thailand

When: August 28–30, 2013

65th Annual Meeting of the Society for Biotechnology, Japan

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Where: Hiroshima, Japan

When: September 18–20, 2013

Asian Congress on Biotechnology

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Where: New Delhi, India

When: December 15–19, 2013


Food Biochemistry and Food Processing, 2nd Edition

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Editors: Benjamin K. Simpson et al.

ISBN: 978-0-8138-0874-1

In Food Biochemistry and Food Processing, Second Edition, the editors brought together more than fifty acclaimed academics and industry professionals from around the world to create this fully revised and updated edition. This book is an indispensable reference and text on food biochemistry and the ever-increasing developments in the biotechnology of food processing.

Marine Microbiology – Bioactive Compounds and Biotechnological Applications

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Editor: Se-Kwon Kim

ISBN: 978-3-527-33327-1

This unique reference systematically covers the technology behind high-value compounds for use as pharmaceuticals, nutraceuticals or cosmetics, from prospecting to production issues.

Kirk-Othmer Chemical Technology of Cosmetics

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Editor: Kirk-Othmer

ISBN: 978-1-118-40692-2

Based on Wiley's renowned Kirk-Othmer Encyclopedia of Chemical Technology, this book makes sense of a vast group of consumer products designed to improve the health, cleanliness, and physical appearance of the human exterior.

Improving Crop Productivity in Sustainable Agriculture

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Editors: Narendra Tuteja, Sarvajeet Singh Gill and Renu Tuteja

ISBN: 978-3-527-33242-7

An up-to-date overview of current progress in improving crop quality and quantity using modern methods. With a particular emphasis on genetic engineering, this text focusses on crop improvement under adverse conditions, paying special attention to such staple crops as rice, maize, and pulses.

Upstream Industrial Biotechnology

2 Volume Set

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Editor: Michael C. Flickinger

ISBN: 978-1-1181-3123-7

Downstream Industrial Biotechnology: Recovery and Purification

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Editor: Michael C. Flickinger

ISBN: 978-1-1181-3124-4

Based on Wiley's Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, this volume features fifty articles that provide information on down- stream recovery of cells and protein capture; process development and facility design; equipment; PAT in downstream processes; downstream cGMP operations; and regulatory compliance.