Applications for Synthetic Biology in Industrial Biotechnology

Friday, 29 November 2013

This is a Euroscicon Small Conference,  an outline of the day can be found at

Applications for Synthetic Biology in Industrial Biotechnology
Friday, 29 November 2013 09:00 - 17:00

Cineworld: The O2
Peninsula Square
SE10 0DX
United Kingdom

Map and Directions
With their provenance as an excellent source of pharmaceutical, neutraceutical and health promoting chemistries, plant natural products are an attractive target for biotechnological development for industrialization  so as to make them more widely available.  To realize this potential, two strategies are currently being employed whereby the associated metabolic pathways are engineered in planta, or are ectopically expressed in microbial hosts and produced through fermentation.   In both cases it is clear that recent developments in genetics, and our understanding of metabolism are providing us with unprecedented tools to fast-track these ambitions.  In addition, the advent of synthetic biology, where approaches more commonly employed in engineering are applied to design and optimize bioprocesses has much to offer industrial biotechnology in the future.

In this meeting a series of metabolic engineering programs  representing each of the differing strategies for natural product biosynthesis will be presented and the potential merits of plant Vs microbial industrial biotechnology discussed, along with projections as to how each might benefit from synthetic biology based approaches.  In addition to reviewing the latest development in plant natural product biochemistry and molecular biology, the meeting will be formative in shaping thinking as to how and where new approaches like synthetic biology can be best applied in industrial biotechnology in the coming years. This meeting will also include a meeting of the High Value Chemicals from Plants Network.

This event has CPD accreditation and is part of
  The 2013 BioProcessing Summit

Meeting Chairs:  Professor Robert Edwards, Chief Scientist, The Food and Environment Research Agency, UK. Professor Ian Graham, CNAP Director and Weston Chair of Biochemical Genetics, University of York, UK. Professor Gary Loake, The University of Edinburgh, Scotland, UK.

9:00 – 9:25    Registration

9:25 – 9:30    Introduction by the Chair:  Professor Robert Edwards, Chief Scientist, The Food and Environment Research Agency, UK

9:30 – 10:00  Building novel isoquinolines with synthetic plant enzymes
Professor John Ward, University College London, UK
Alkaloids are a large and diverse family of nitrogen-containing compounds, many of which are used as pharmaceuticals and they represent a huge repository of functional chemical space. We are using the enzyme (S)-norcoclaurine synthase (NCS) which carries out the key first coupling step in the pathway that generates the tetrahydroisoquinolines. The enzyme catalyses a Pictet-Spengler reaction between arylethylamines and aldehydes, generating a chiral centre. Synthetic versions of the enzyme from several plant species have been designed and expressed in
E. coli. The mechanism of the recombinant NCS is being elucidated and mutations of the Coptis japonica and Thalictrum flavum NCS enzymes have been used to make novel benzyl and aliphatic tetrahydroisoquinolines.

10:00 – 10:30  Cultured cambial meristematic cells as a source of plant natural products Professor Gary Loake, The University of Edinburgh, Scotland, UK
A plethora of important, chemically diverse natural products are derived from plants. In principle, plant cell culture offers an attractive option for producing many of these compounds. However, it is often not commercially viable because of difficulties associated with culturing dedifferentiated plant cells (DDCs) on an industrial scale. To bypass the dedifferentiation step, we isolated and cultured innately undifferentiated cambial meristematic cells (CMCs). Using a combination of deep sequencing technologies, we identified marker genes and transcriptional programs consistent with a stem cell identity. This notion was further supported by the morphology of CMCs, their hypersensitivity to γ-irradiation and radiomimetic drugs and their ability to differentiate at high frequency. Suspension culture of CMCs derived from
Taxus cuspidata, the source of the key anticancer drug, paclitaxel (Taxol), circumvented obstacles routinely associated with the commercial growth of DDCs. These cells may provide a cost-effective and environmentally friendly platform for sustainable production of a variety of important plant natural products.

10:30 – 10:55    Speakers’ photo then mid-morning break and trade show

10:55– 11:00     Introduction by the Chair:  Professor Ian Graham, CNAP Director and Weston Chair of Biochemical Genetics, University of York, UK

11:00 – 11:30    Engineering flavonoid metabolism in yeast
Robert Edwards , Chief Scientist, The Food and Environment Research Agency, UK Phenylpropanoids are simple aromatic natural products found in all plants which are used as the building blocks for a wide range of polyphenols including a diverse array of flavonoids with activities as diverse as dietary cytoprotectants, colourants and flavour enhancers.  Using polyprotein technology we have engineered bakers’ yeast to transform readily available phenylpropanoids left over from brewing and biofuel production into high value flavonoids, including glycosylated derivatives with uses as artificial sweeteners. The approach adopted shows the value of effectively transferring plant metabolic pathways into non-natural hosts to extend the diversity of end products which can be generated in useful quantities. 

11:30 – 12:00     Metabolic engineering of high value lipids in transgenic plants
Professor Johnathan Napier,
Rothamsted Research Limited, Hertfordshire, UK
Using genetic engineering it is now possible to generate transgenic plants which have the capacity to synthesise high value fatty acids such as the omega-3 long chain polyunsaturates. 

12:00 – 12:20     Oral Presentation:

O. Sayanova
, M. Hamilton, R. P. Haslam, J. A. Napier.
Rothamsted Research, Harpenden, Herts, AL5 2JQ, UK

12:20– 13:30      Lunch and trade show

13:30– 14:30      High Value Chemicals from Plants Network Meeting

14:30– 15:00      Engineering polyphenols in tomatoes
Professor Cathie Martin, Theme Leader Plant Natural Products, John Innes Centre, UK Understanding the complex relationship between diet and health has become key to developing preventive strategies to reduce the rising incidence of chronic disease, globally. As an example of how this new experimental field can work I will describe our work on enrichment of tomatoes with different polyphenolic bioactives, for comparative nutritional studies. We have produced tomatoes enriched in anthocyanins, flavonols, resveratrol and isoflavones. Experiments using animal disease models have shown the anthocyanin-enriched tomatoes to have anticancer and anti-inflammatory properties. Cell-based assays have provided insight into the mechanisms of action of anthocyanin bioactives. Ongoing preclinical studies address how well other polyphenols compare to anthocyanins (in a common food matrix) in a cardiovascular disease model. Human intervention studies are also about to begin.

15:00 - 15:25    Afternoon Tea/Coffee and trade show

15:25 – 15:30   Introduction by the Chair:  Professor Gary Loake, The University of Edinburgh, Scotland, UK

15:30 – 16:00      A ten gene cluster responsible for synthesis of the anticancer alkaloid noscapine in opium poppy
Professor Ian Graham,
CNAP Director and Weston Chair of Biochemical Genetics, University of York, UK
Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase and induces apoptosis in dividing human cells. We recently discovered a cluster of 10 genes encoding five distinct enzyme classes that are responsible for noscapine production in poppy (Winzer et al., Science, 2012). Virus induced gene silencing resulted in accumulation of pathway intermediates allowing a novel biosynthetic pathway to be proposed. This advance adds to our knowledge of gene clusters in plants and will enable improvement in commercial production of noscapine and related bioactive molecules.

16:00 – 16:30     Genome mining and metabolic engineering for triterpene synthesis Professor Anne Osbourn, Associate Research Director, John Innes Centre, UK
Plants produce a huge array of natural products, many of which are specialised metabolites associated with particular
species.These secondary metabolites often have important ecological functions.  Although the ability of plants to perform in vivo combinatorial chemistry by mixing, matching and evolving the genes required for different secondary metabolite biosynthetic pathways is likely to have been critical for survival and diversification of the Plant Kingdom we know very little about the mechanisms underpinning this process.  This talk will focus on plant natural product function and synthesis, the origins of metabolic diversity and potential for metabolic engineering, drawing on our research on triterpene synthesis in crop and model plants.  Triterpenes have important ecological and agronomic functions, contributing to pest and pathogen resistance and to food quality in crop plants.  They also have a wide range of commercial applications in the food, cosmetics and pharmaceutical sectors.

16:30 - 17:00        Chairmen’s summing up and Close of Meeting

Keywords: High value products; metabolic engineering; non-food crops; biorefining; natural products, monoclonal antibodies, hybridoma, recombinant protein, monoclonal antibody, production, hollow fiber., hollow  fiber, double membrane, cell culture; viral vaccine; gene therapy; stem cell; scale-up, Biorefining, Design of Experiments, process scale-up, industrial biotechnology, biorenewable chemicals,  enzymes, Phenylpropanoids, cytoprotectants, flavonoid, yeast, Transgenic plants, omega-3 polyunsaturates, metabolic engineering, Metabolic engineering; terpenes; synthetic biology; plant protection; anti-cancer drugs, Alkaloids, Papaver somniferum, gene cluster, biochemical pathway, Polyphenols, tomato, metabolic engineering, cancer, preventive therapy

About the Chairs:
Robert Edwards is the Chief Scientist at the Food and Environment Research Agency (Fera) and also runs a research group at the University of York in the Centre for Novel Agricultural Products, where he has a Chair in Crop Protection. He was formerly Head of Biology at Durham University, with 26 years of postdoctoral experience as a Plant Biochemist working in the public and private sectors in the UK and USA.  As co-ordinator of the cross Research Council-funded network ‘Synthetic Plant Products for Industry’ he has been working with industrialists and academics on applications for synthetic biology in the improvement and utilisation of crop plants in biorefining.  Research interests in metabolic  engineering include manipulating high value flavonoid production and the biotransformation of synthetic chemicals.  Expertise in natural products at Fera includes state-of-the-art facilities in measuring a wide range of analytes in food and environmental samples and research programmes in biorenewables.
Ian Graham holds the Weston Chair of Biochemical Genetics and is the Director of the Centre for Novel Agricultural Products (CNAP) at the University of York. His research interests focus on seed biology and metabolic engineering of novel oils and other high value chemicals. Current projects range from the development of novel oilcrops such as Jatropha curcas to medicinal plants such as Artemisia annua that produces the anti-malarial compound artemisinin and opium poppy that produces analgesics and other compounds for the pharmaceutical industry. Funding for Ian’s research comes from a range of sources including industry, UK Government, EU and various charities.

Gary Loake’s research aims to understand the molecular mechanisms underpinning plant disease and resistance. 1996  Joined University of Edinburgh, 1995-1996  Senior Postdoctoral Fellow, The Plant Laboratory, University of York, UK, 1991-1994 Salk-Noble Plant Biology Fellow, Salk Institute, California, USA, 1990-1991 Salk-Noble Plant Biology Fellow, Samuel Robert Noble Foundation, 1990 Ph.D. University of Durham, Durham, UK

About the Speakers:

John Ward is Professor of Synthetic Biology for Bioprocessing in the Advanced Centre for Biochemical Engineering at University College London.  He and colleagues at UCL have used enzymes such as transaminases, transketolase, Bayer-Villiger monooxygenase, cytochrome P450 and norcoclaurine synthase to make chiral compounds. He has developed biocatalysis and synthetic biology routes to chiral compounds such as aminodiols and tetrahydroisoquinolines.

Johnathan A. Napier’s research on the biosynthesis of polyunsaturated fatty acids has delivered some of the key advances in the last 15 years. He obtained his BSc from the University of Nottingham, followed by a PhD in plant biochemistry from King’s College, London. He carried out post-doctoral research in the Department of Plant Sciences, University of Cambridge, then taking up a position at Long Ashton Research Station in Bristol. His research group relocated to Rothamsted Research in 2003 where he is currently Institute Assistant Director and Programme Leader. Johnathan is also an Affiliated Lecturer at the University of Cambridge.

Cathie Martin’s interests span the entire spectrum of plant biology, from the fundamental to the applied ends. Recently, she has engineered phenylpropanoid metabolism using transcription factors to improve foods and demonstrated that elevated dietary anthocyanin levels in food extend the life span of cancer prone mice by 30%  and afford cardioprotection. Cathie has co-ordinated two EU projects, FLORA and ATHENA, which linked the activities of plant geneticists, metabolic engineers, chemists, nutritionalists, food technologists, cardiologists, epidemiologists to develop model foods with defined levels of flavonoid bioactives and to investigate the health promoting effects of these foods.

Anne Osbourn is Associate Research Director of the John Innes Centre, Norwich.  Her research focuses on plant natural products - function, synthesis and metabolic diversification.  She is an author of over 100 peer-reviewed scientific publications and recently co-edited a comprehensive textbook on plant-derived natural products [Lanzotti V & Osbourn A. (2009) Plant-derived natural products – Synthesis, function and application. Springer, New York, USA]. She has also developed and co-ordinates the Science, Art and Writing (SAW) initiative, a cross-curricular science education programme for schools (


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