BIONEXGEN Overview
Edition 1, December 2011
Developing the Next Generation of Biocatalysts for Industrial Chemical Synthesis
A Framework 7 supported
project, this first edition of
the project newsletter aims
to provide an introduction
to the project & partners
and highlight relevant
research and technology
developments.
and compounds for anti-oxidants,
antifreeze and coolants. In 2007
the total global sales of products
made by biotechnology processes
totalled €48bn and owing to a
number of trends and drivers,
including price and availability of
crude oil, this sector is expected
to grow significantly, with some
estimations being in excess of
€300bn by 2025.
Industrial Biotechnology is
defined as: ‘The use of biological
substances (including plants, algae,
marine life, fungi, micro-organisms)
for the processing and production
of enzymes, chemicals, materials
and energy’.
It is therefore already an exciting
time for Industrial Biotechnology
in the chemical industry but,
as more target products are
identified, further breakthroughs in
technology will be required for the
full potential to be exploited.
The use of Industrial Biotechnology
for the production of chemicals
offers a range of advantages for
consumers and broader society
including:
BIONEXGEN aims to provide such
breakthroughs. A flagship EU
collaborative research project, the
goal of BIONEXGEN is to develop
the next generation of biocatalysts
to be used for eco-efficient
manufacturing processes in the
chemical industry.
• Cheaper, more readily available products, in particular pharmaceuticals and cosmetics
• Access to natural and / or eco-
friendly products
• Products with often reduced CO2 footprint and safer manufacturing routes
Biotechnology has been used
for hundreds of years in the
production of bread, cheese and
beer and its industrial application
to produce e.g. antibiotics and
sweeteners has been established
since the 1960s. However, recent
developments in synthetic biology
have allowed a new wave of
products to be commercialised
and examples of products of
Industrial Biotechnology now
include: natural flavourings e.g.
vanilla, cocoa butter for chocolates,
food packaging, steroids and
vitamins, cosmetic moisturizers
A number of key technology
fields were previously identified
with industrial input and included
amine synthesis, polymers from
renewable resources, glycoscience
and wider oxidase applications (e.g.
fine chemicals). BIONEXGEN will
use these industrially identified
products and product family leads
to develop biocatalysts which can
be used routinely in economically
viable industrial production.
With a total project budget of over
€10m, the research objectives for
BIONEXGEN include:
• The design and optimisation of enzymes to be used in synthetic chemistry
• The development of modified microorganisms which are resistant to heat, pressure or low pH, suitable for use in industrial production
• The integration of these biotechnological steps into applied chemical processes
BIONEXGEN Overview
In this issue:
BIONEXGEN Overview
01 Introduction to BIONEXGEN
03 Update on BIONEXGEN Project
BIONEXGEN Work
04 Early Success in BIONEXGENA nutraceutical now available for
testing
05 Industrial Biotechnology in the
Press
BIONEXGEN Technology Platforms
06 Technology Platforms – Enzyme
Immobilisation
Meet the BIONEXGEN Researchers
08 Meet the researchers from three
of the project participants
BIONEXGEN Overview
Co-ordinated by The University of Manchester, the
BIONEXGEN project consortium consists of 17 partners from
9 European countries:
The University of Manchester, United Kingdom
The University of Stuttgart, Germany
Technical University of Denmark (DTU), Denmark
The Institute of Microbiology of the Czech Academy of Sciences (IMIC),
Czech Republic
University of Groningen, Netherlands
CLEA Technologies BV, Netherlands
EntreChem SL, Spain
University of Oviedo, Spain
GALAB Laboratories GmbH, Germany
Leibniz Institute of Plant Biochemistry, Germany
Austrian Centre of Industrial Biotechnology, (ACIB) Austria
Royal Institute of Technology (KTH), Stockholm, Sweden
LentiKats a.s, Czech Republic
Slovak University of Technology, Slovakia
BASF SE, Germany
University College London (UCL), United Kingdom
Chemistry Innovation Ltd, United Kingdom
For more information on the BIONEXGEN project visit:
http://bionexgen-fp7.eu/
BIONEXGEN Research is split into 8 multi-disciplinary themes:
Product Areas
Industrial Amine Synthesis
Amines are vital for the industrial
synthesis of pharmaceuticals, bulk
and speciality chemicals.
Renewable Resources in Novel
Polymer Chemistry
Polymers are by far the largest
volume of chemical products on
the market with strong market
pull for bio-based polymers in
many industries e.g. automotive,
packaging, construction, cosmetics
and detergents.
Applications of Enzymes to
Glycoscience
Enzymatic methods have great
synthetic appeal for this traditionally
challenging area of chemistry
producing molecules which can
be used for controlling health and
disease and in food and feed.
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Industrial Applications of Oxidases
Development of efficient and robust
oxidative biocatalysts and the
technology for performing selective
oxidations that will be valuable
for use in the pharmaceutical, fine
chemical and food industries.
Underpinning Technology
Fermentation Science
A focus on efficient production
strains and high density
fermentation techniques which are
critical to economic performance.
Biocatalyst Supports and
Chemocatalysts Integration
Application of biocatalyst
immobilisation technology to utilise
biocatalysts in industrial chemical
synthesis.
Bioprocess and Chemical
Engineering
Process engineering research
to develop and implement new
biocatalytic processes in industry.
Economic, Environmental and Life
Cycle Analysis
Developing a simplified
methodology for quick and reliable
quantitative assessment.
BIONEXGEN Update
A kick-off meeting, Biotrans
conference and the first
BIONEXGEN review meeting,
there has been plenty of
activity in the first 9 months
of the project.
The BIONEXGEN project started
in February 2011 and from the first
kick-off meeting, expectations
were high. Attending the meeting
in Brussels, Alfredo Aguilar
Romanillos1, DG RTD, European
Commission said the project
was unique, receiving the largest
budget of any FP7 projects in the
KBBE area to date. BIONEXGEN
is expected to have real impact in
the field of Industrial Biotechnology
with tangible benefits for European
SMEs working in the area.
The project team have quickly built
up excellent working relationships
and made substantial progress
towards the initial goals. The first
6 month report was submitted
to the Commission on time in
September and feedback from the
Project Officer was very positive
with all the initial milestones and
deliverables being achieved on
time.
In early October many of the
project researchers attended the
Biotrans 2011 Conference in Sicily
with presentations provided by
BIONEXGEN partners University of
Manchester, IMIC, Royal Institute of
Technology (KTH), The University
of Stuttgart and ACIB. Commenting
on the conference Dr Kirk Malone,
Project Manager of BIONEXGEN
said “The conference provided an
ideal backdrop for BIONEXGEN
due to the quality and breadth of the
science being discussed. It allowed
our researchers to network with
their contemporaries from across
the globe, and gave an international
stage to present some of our initial
research success. We were also
able to have a small BIONEXGEN
project meeting due to the number of
partners in attendance. Overall it was
a hugely successful conference, and
the University of Manchester looks
forward to hosting the event in 2013
(although we can’t guarantee the
Sicilian sun and wine!)”
October 2011 saw BASF,
Ludwigshafen host the first
review meeting for BIONEXGEN.
Attended by over 40 researchers
representing all 17 project partners
the two-day meeting provided
time for project updates, technical
discussions, and detailed work
programme break-out meetings.
Ensuring opportunity for the
project team to get acquainted,
BASF hosted an excellent tour of
their Wine Cellar at Ludwigshafen
and subsequent dinner. The
impressive initial results presented
provided plenty of discussion
and the energy and momentum
created by the meeting will surely
carry through to the next meeting.
Thanks to Dr Kai Baldenius and
Dr Vaidotas Navickas of BASF for
such excellent organisation of the
meeting.
1 Head of Unit Biotechnology, Directorate Biotechnologies,
Agriculture and Food.
BIONEXGEN Partner Logos
The BIONEXGEN newsletter edition 1
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BIONEXGEN Work
CASE STUDY OF
BIONEXGEN SUCCESS Production of Isoquercitrin
The BIONEXGEN project has
facilitated a new process for the
production of Isoquercitrin, a
nutraceutical. Avoiding difficult
extraction processes, this novel
route based on ‘green chemistry’
principles uses an enzyme
expressed in yeast. Samples are
currently being evaluated within
the consortium.
Isoquercitrin, a flavonoid naturally
occurring in vegetables and fruits,
is known to be active against
many human health conditions
including: cardiovascular disease,
asthma, stroke, capillary fragility,
arteriosclerosis, trauma, oxidative
stress, hypertension, elevated
cholesterol, elevated triglycerides,
hyperglycemia, type II diabetes,
obesity and related disorders, and
Alzheimer’s disease. A strong
antioxidant and chemoprotectant,
isoquercitrin is devoid of the
unwanted side effects of quercetin
(its aglycon) in addition to having
better solubility in water and
higher bioavailability. Isoquercitrin
therefore has a good potential
for application in nutraceuticals,
adjuvant therapy of cancer, and in
dermatological preparations and
is currently being evaluated in
research trials. However, despite
its relatively high content in e.g.
apples, onion (ca 50 - 300 mg/kg)
its isolation is technically extremely
complicated, resulting in a very
high price and thus limiting trials
for wider applications.
Within the BIONEXGEN project,
Professor Kren and his team at
Inst. of Microbiology, Prague, CZ
(IMIC), have been able to produce
high yields of isoquercitrin from
rutin, a naturally occurring product
available from Brazilian tree fava
d’anta (Dimorphandra mollis),
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BIONEXGEN Work
using an enzyme sequenced and
expressed in yeast.
extremely useful for further scaleup, for which experiments are now
under way and immobilization into
the CLEA system is also under
preparation.
Both the enzyme (wild or cloned
expressed in yeast) and the product
(isoquercitrin) are available to all
consortium partners for further
evaluation.
Fig. 1 Rutin (1) derhamnosylation to
Isoquercetin (2).
Their procedure is based on ‘green
chemistry’ principles without any
toxic additives. Moreover, it is a
“waste-free” procedure since the
biotransformation medium can be
recycled and used as production
medium for the fermentation
stage. The biotransformation
uses a known enzyme, previously
employed to enhance grape juice
aroma and wine aromas. The
enzyme has been found to exhibit
exceptional biochemical properties;
thermo- and alkali-tolerant,
enabling long-term operation at
70˚C and pH 8.0.
This procedure enables very high
volumetric productivity (up to 300
g/L) and yields the product devoid
of highly unwanted quercetin.
Commenting on the work Prof Kren
said “The significant advantage of
our expression system consists in
shorter production times, up to fourfold
increase of enzyme yields and the
absence of unwanted β-D-glucosidase
as compared to the native production
system.”
The BIONEXGEN project
dramatically speeded up the
research on this enzyme and
allowed scale-up experiments to
be done in collaboration with two
partners (LentiKats and Slovak
Technical University, in Bratislava)
recently. Immobilization into the
LentiKats system proved to be
For more information contact:
Prof. Dr. Vladimir Kren
Institute of Microbiology,
Academy of Sciences of the Czech
Republic
Laboratory of Biotransformation
National Centre of Biocatalysis and
Biotransformation
Videnska 1083
CZ 142 20 Praha 4, Czech Republic
Tel. (+420) 296 442 510, 296 442 569
Fax. (+420) 296 442 509, 296 445 743
e-mail: [email protected];
http://www.biomed.cas.cz/mbu/
biotrans
In the Press
This section highlights the
technically relevant publications
from within the consortium
and a few of the recent
global announcements of
Industrial Biotechnology and
its commercialisation in the
chemical industry.
BIONEXGEN participants’ selected
recent publications:
Recent progress in industrial
biocatalysis, Bettina M. Nestl,
Bernd A. Nebel and Bernhard
Hauer, Current Opinion in Chemical
Biology, 2011, 15, 187–193
This review describes some of the
recent innovative developments
in the rapidly growing field of
enzymatic catalysis, with particular
focus on potential applications in
biotransformations.
This work describes the
combination of molecular biology
and bioprocess techniques for
the rapid evaluation of multi-step
enzymatic syntheses. The approach
is illustrated for the asymmetric
synthesis of chiral aminoalcohols
combining transketolase and
transaminase enzymes.
Enantioselective Oxidation of C-O
and C-N Bonds Using Oxidases,
Nicholas J. Turner, Chemical
Reviews, 2011, 111, 4073–4087
Oxidation reactions represent a
cornerstone of organic chemistry,
providing access to a range of
functional groups that allow further
functionalisation of building
blocks used in synthesis. This
review focuses on the biocatalytic
oxidation of alcohols and amine
functional groups.
Multienzyme-Catalyzed Processes:
Next-Generation Biocatalysis,
Paloma A. Santacoloma, Gürkan
Sin, Krist V. Gernaey, and John M.
Woodley, Organic Process Research
& Development, 2011, 15, 203–212
Most biocatalysis studies have
been carried out using single
enzymes, but multiple enzyme
mixtures are attracting more
interest for the production of many
compounds at an industrial level.
In this review, a classification of
multienzyme-catalyzed processes
is proposed. Special emphasis
is placed on the description of
multienzyme ex-vivo systems
where several reactions are carried
out by a combination of enzymes
acting outside the cell
A toolbox approach for the rapid
evaluation of multi-step enzymatic
syntheses comprising a ‘mix and
match’ E. coli expression system
with microscale experimentation,
Rios-Solis, L., Halim, M., Cázares,
A., Morris, P., Ward, J.M., Hailes,
H.C., Dalby, P.A., Baganz, F. and
Lye, G.J. (2011). Biocat. Biotrans.,
29(5): 192-203.
An automated microscale platform
for evaluation and optimisation of
oxidative bioconversion processes,
Baboo, J.Z., Galman, J.L., Lye, G.J.,
Ward, J.M., Hailes, H.C., Micheletti,
M. (2011). Biotechnol. Prog., in
press.
The development of advanced
biocatalytic processes requires
the evaluation of a large number
of bioprocess conditions. This
paper describes an automated,
high-throughput platform for the
rapid optimisation of oxidative
bioconversions and the generation
of scaleable bioprocess design
data.
Industrial Biotechnology News
OECD Report on Future Prospects
for Industrial Biotechnology
Published in October, this report
builds on a number of workshops
and reports from 2010/2011 and
summaries the potential future for
the OECD regions. Concluding
that “The outlook is promising:
the convergence of industrial
biotechnology drivers with the
unprecedented progress in the
biological sciences is timely. The
barriers are many; they must be
tackled by regional, national and
internationally harmonised policy.”
The report can be viewed online
here or can be purchased for €33.
BASF and Purac to produce biobased succinic acid.
BIONEXGEN partners, BASF have
announced they plan to enter into a
joint venture with CSM subsidiary
Purac, to produce bio-based
succinic acid. Aiming to be the first
commercial producer in the market,
they intend to start a 25,000 ton
fermentation production plant in
Barcelona by 2013. Finding uses
as a chemical intermediate, solvent,
in polyurethanes, plasticisers and
increasingly bioplastics, demand
for succinic acid is expected
to grow strongly. Read the full
announcement here
Toyota use 80% bioplastics in new
model
Toyota has revealed that the interior
of the new Sai Hybrid model will
consist of 80% materials derived
from sugar cane. The bioplastics
used will be in exposed surfaces,
including seats, trims and carpets.
The use of bio-derived monomers
in its bio-polyethylene terephthalate
(bio-PET) gives materials that
perform on cost and properties and
they now appear to be replacing
the use of fossil derived ethylene
glycol.
Toyota have been working towards
their totally renewable material
derived car for a number of years
now and this is another step
forward.
Michelin aims to use bio-isoprene
for its tyres.
Amyris and Michelin have
announced a collaboration to
commercialise renewable isoprene
in the production of tyres.
This follows in the steps of the
Goodyear/Genencor agreement
announced a few years ago. With
Amyris expecting bio-isoprene
to be commercialised in 2015,
Michelin is committed to taking the
material on a ten-year basis. The
non-exclusive agreement allows
Amyris to provide its renewable
isoprene to other customers. Read
more here.
The BIONEXGEN newsletter edition 1
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BIONEXGEN Technology Platforms
(kgs product per kg enzyme) owing
to the large amount of non-catalytic
ballast (often > 95% of the total
mass).
Technology Platforms
Enzyme Immobilization
• lack of operational stability
• lack of storage stability
• cumbersome recovery and recycling
• product contamination
If the use of enzymes as
biocatalysts in the production
of chemicals is to be fully
exploited these obstacles must be
overcome. Immobilization of an
enzyme by binding to a support,
such as an ion exchange resin
or silica, or encapsulation in an
inert matrix such as a silica sol
gel is well known and leads to
improved storage and operational
stability and provides for its facile
separation and re-use.
However, these traditional
immobilization strategies can be
costly and afford carrier-bound
enzymes with low productivities
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Cross-linked enzymes, produced
by mixing an aqueous solution
of the enzyme with an aqueous
solution of glutaraldehyde, were
already known in the 1960’s and
afforded carrier-free immobilized
enzymes with high productivities.
However, these generally had low
activity, poor reproducibility, low
stability and shelf life, and were
difficult to handle. Consequently,
carrier-bound enzymes became the
method of choice for the next three
decades.
In the early 1990s Altus Biologics
introduced the use of crosslinked enzyme crystals (CLECs)
as industrial biocatalysts. The
methodology was applicable to a
wide variety of enzymes and CLECs
exhibited excellent operational
stability, controllable particle size
coupled with high productivity and
facile recovery and re-use, making
them ideally suited to industrial
biocatalysis. However, they had
one inherent limitation: the need to
crystallize the enzyme, a laborious
procedure requiring enzyme of high
purity which in practice translates
to relatively high costs.
More recently, ‘smart’ magnetic
CLEAs have been prepared by
conducting the cross-linking in
the presence of functionalized
magnetic nanoparticles. These
mCLEAs can be separated by
magnetic decantation or can be
used in a magnetically stabilized
fluidized bed potentially leading
to novel combinations of
bioconversions and downstream
processing. A further elaboration
of the CLEA methodology is the
preparation of combi-CLEAs, from
mixtures of two or more enzymes,
for use in multi-enzyme cascade
processes.
CLEA Immobilization
Despite recent advancements in
the development of biocatalysts,
enzymes are complex, highly
sensitive molecules with unique
three-dimensional structures. When
exposed to certain conditions, e.g.
elevated temperatures or organic
solvents, this structure can be
denatured or unfolded resulting
in significant activity loss. Other
factors affecting the efficiency of
enzymes in full-scale chemical
production can include:
new class of immobilized enzymes
called cross-linked enzyme
aggregates (CLEA®s).
The CLEA methodology essentially
combines two unit processes,
purification and immobilization,
into a single operation. In principle,
one can take the crude enzyme
extract from fermentation broth
and produce the immobilized
enzyme in one simple operation.
A variation on this theme involves
performing the cross-linking in
the presence of a monomer that
undergoes polymerization under
these conditions. This results in
the formation of a CLEA-polymer
composite with tunable physical
properties. For example, if the
cross-linking is performed in the
presence of a siloxane the latter
undergoes polymerization to afford
a CLEA-silica composite. The
hydrophobic/hydrophilic properties
and particle size of the latter can
be tailored by manipulating the
structure of the siloxane used.
Within the BIONEXGEN project
two different immobilization
technologies will be employed and
evaluated, CLEA and LentiKats. In
this edition we learn more about the
CLEA immobilization technology.
Immobilization of enzymes
improves storage and operational
stability and facilitates recovery
and recycling of the biocatalyst.
CLEA technology involves crosslinking of the crude enzyme
resulting in high productivities.
With potential to add functionality
e.g. hydrophobicity or magnetic
properties this technology has
potential benefits for many novel
biotransformations.
BIONEXGEN Technology Platforms
Several years ago, Roger Sheldon
and a team of scientists at Delft
University of Technology reasoned
that crystallization could perhaps
be replaced by precipitation of the
enzyme from aqueous buffer, a
simpler and less expensive method
not requiring highly pure enzymes.
This led to the development of a
Protease-CLEA (free-flowing powder)
Benefits of CLEAs
CLEAs have many economic and
environmental benefits in the
context of industrial biocatalysis.
They are easily prepared from
crude enzyme extracts and the
costs of (often expensive) carriers
are circumvented. They generally
exhibit improved storage and
operational stability towards
denaturation by heat, organic
solvents and autoproteolysis and
are stable towards leaching in
aqueous media. Furthermore, they
have high catalyst productivities
(kgs product per kg biocatalyst)
and are easy to recover and
recycle. CLEAs are highly porous
materials and diffusional limitations
are generally not observed
with standard CLEAs in typical
bioconversions. Moreover, the
particle size is amenable to tuning
with optimum rates being observed
with smaller particles but practical
considerations, e.g. ease of
filtration, often dictating the use of
larger particles.
Comparison of immobilization techniques
The proprietary CLEA methodology
has been commercialized by CLEA
Technologies and CLEAs from a
variety of commercially available
enzymes are already for sale
on the open market (see www.
cleatechnologies.com) as well
as custom CLEAs from enzymes
provided by clients on an exclusive
basis.
Work within the BIONEXGEN
project will ascertain whether
this innovative and cost effective
immobilization technology is
applicable to the next generation
of biocatalysts and subsequent
chemistries.
For more information contact Roger
Sheldon ([email protected])
The BIONEXGEN newsletter edition 1
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The BIONEXGEN Researchers
The BIONEXGEN Researchers
Meet the BIONEXGEN
researchers
This section of the newsletter
will introduce the BIONEXGEN
researchers working around
Europe. In this edition we meet
the researchers from University
of Manchester, University of
Stuttgart and Entrechem.
Dr Rachel Heath
The University of Manchester
The University of Manchester team
is led by Professor Nick Turner
and Professor Sabine Flitsch. Prof.
Turner is the Project Coordinator
of BIONEXGEN and, as Director
of the Centre of Excellence in
Biocatalysis (CoEBio3), has
had considerable experience of
heading large European research
consortia. He is also a co-founder
of the biotechnology company
Ingenza, and has recently set
up the biocatalyst screening
company Discovery Biocatalysts.
His research group are primarily
focussed on the use of enzymes
as biocatalysts for industrially
relevant organic synthesis. Prof.
Flitsch leads the glycoscience and
oligosaccharide synthesis work in
BIONEXGEN. Her research group is
highly interdisciplinary, consisting
of chemists, enzymologists and
molecular biologists carrying
out research in the areas of
glycoscience and biocatalysis. Prof.
Flitsch also has great experience of
leading scientific consortia, being
the Coordinator of the EU projects
EuroGlycoArrays and GlycoBioM.
Laboratory research in Manchester
is being carried out by Dr. Miguel
De Abreu and Dr. Rachel Heath.
Miguel studied biochemistry at
the University of Miami, followed
by a PhD in molecular biology
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Professor Sabine Flitsch
at the Severo Ochoa Centre of
Molecular Biology (Autonomous
University of Madrid, Spain).
His focus in Manchester is on
the design and development of
glycosyltransferases to create
new types of oligosaccharides
for commercial uses. Rachel has
a background in chemistry and
a PhD in bioinorganic chemistry
from the University of Oxford. She
then worked for Syngenta where
she broadened her skill set with
molecular biology techniques
and assay development. Having
returned to academia, she is
applying her experience to the
development of biocatalysts for
amine synthesis.
Several more researchers are going
to join the team in Manchester in
the next few months.
Dr. Friedemann Leipold and Dr.
Professor Nick Turner
Elaine O’Reilly will join Prof.
Turner’s project in January 2012
and Dr. Peter Both and Dr. Anthony
Green will join Prof. Sabine Flitsch.
Friedemann studied Biochemistry
at the Ernst-Moritz-Arndt University
Greifswald, where he is currently
finishing a PhD on the subject
Baeyer-Villiger monooxygenase
enzymes. Elaine studied Chemistry
at University College Dublin (UCD)
and carried out her PhD research
there focusing on the synthesis of
non-proteinogenic amino acids with
biological applications. Her focus
in Manchester will be developing
Cytochrome P450 biocatalysts
with broad substrate scope and
the ability to catalyse a range of
synthetically challenging oxidation
reactions.
Peter did a joint PhD in molecular
and structural biology at CERMAV
CNRS (Joseph Fourier University,
Grenoble, France) and the
Institute of Chemistry, Center for
glycomics of the Slovak Academy
of Sciences. He then worked at the
University of Natural Resources
and Applied Life Sciences,
Vienna, Austria, where he studied
several glycosyltransferases and
mannosidases using the tools of
molecular biology. Anthony studied
chemistry at the University of
Nottingham, followed by a PhD in
organic chemistry at the University
of Manchester. He has recently
completed a year’s post-doctoral
research with Prof. Flitsch and was
recruited onto the BIONEXGEN
project for his synthetic chemistry
knowledge.
The initial BIONEXGEN project
was conceived and constructed in
Manchester by Dr. John Whittall,
who invited a group of Europe’s
leading academic and industrial
biotechnology partners to join the
project at the application stage.
John’s role within CoEBio3 is to
identify technical opportunities
arising from the biocatalytic
research and he also coordinates
the FP7 programmes. John
previously worked for Stylacats
as Head of Research and before
that Lancaster Synthesis. The
Project Manager of BIONEXGEN
is Dr. Kirk Malone. Kirk completed
his MChem degree and PhD in
organic chemistry at the University
of Edinburgh, and worked as a
medicinal chemist at SmithKline
Beecham Pharmaceuticals. Kirk
is the Research Team Leader
at CoEBio3, experienced with
managing a variety of biocatalysis
research projects at the interface of
academia and industry.
Dr Anthony Green, Dr Miguel De Abbey, Dr Peter Both
Dr John Whittal
Dr Elaine O’Reilly
Dr Kirk Malone
Photo credit to iwouldstay : Flicker
The BIONEXGEN newsletter edition 1
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The BIONEXGEN Researchers
University of Stuttgart
Since 2009, Prof. Dr. Bernhard
Hauer is professor of technical
biochemistry at the Universitaet
Stuttgart, Germany. The main areas
of research are (i) the development,
identification, characterisation and
optimisation of novel enzymes as
biocatalysts for organic synthesis,
(ii) the use of peptides and proteins
for new medical and industrial
applications, (iii) the upscaling of
prokaryotic and eukaryotic proteins
and expression systems to medium
scales, as well as (iv) the study
of the molecular basis of protein
properties using bioinformatic
methods and molecular modelling.
Within the BIONEXGEN project
Bernhard Hauer co-ordinates work
relating to renewable resources
in novel polymer chemistry,
collaborating closely with the
Austrian Centre of Industrial
Biotechnology, Austria and the
Royal Institute of Technology,
Sweden.
The BIONEXGEN Researchers
Bernhard Hauer began his career
at BASF SE in Ludwigshafen,
Germany. At BASF he held a
post as Group Leader within the
biocatalysis and biotransformation
department, followed by an
appointment as Scientific
Director of Biotechnology. In
1996 he performed his scientific
habilitation in the field of molecular
biology at the University of
Heidelberg, Germany. With over
200 publications and patents in the
field of industrial biotechnology,
Bernhard Hauer is very much
part of the international scientific
community.
biotechnology. Two graduates from
the Universitaet Stuttgart, Konrad
Otte, a chemist, and Marko Kirtz,
a technical biologist, strengthen
the team in the BIONEXGEN
project. The PhD students are
co-supervised and advised by Dr.
Janosch Klebensberger, head of
the Molecular Biotechnology group,
and Dr. Bettina Nestl, head of the
Biocatalysis group, at the Institute
of Technical Biochemistry.
The Universitaet Stuttgart team
currently consists of several
highly qualified PhD students
with a different scientific focus
each: Sumire Honda Malca studied
pharmacy and biochemistry in
Peru and joined Bernhard Hauer´s
group after a short stopover at
the Royal Institute of Technology,
Sweden, to finish her Master´s in
From left to right: Marko Kirtz, Sumire
Honda Malca, Dr Bettina Nestl, Konrad Otte,
Dr Janosch Klebensberger
http://bionexgen-fp7.eu
EntreChem SL is an SME focused
on the discovery and development
of new drugs, primarily for
oncology, from bacterial sources
applying metabolic pathway
engineering and biocatalysis.
Formed in 2005 as a spin-off
from the University of Oviedo
(Spain), EntreChem also offers
enantiomerically pure chiral
building blocks, specifically
high optical and chemical purity
amino alcohols and diamines
for medicinal chemistry or
pharmaceutical intermediates.
Within the BIONEXGEN project
Entrechem is involved in
producing enzymes for oxidation
and halogenation reactions and
tasked with this challenge are a
team of three multi-disciplined and
experienced scientists; Dr Javier
González-Sabín, Dr Luz Elena
Núñez and Dr Jesús Cortés.
Dr Bernhard Hauer
10
EntreChem SL
Luz Elena and Jesús role in
the Bionexgen project includes
carrying out the cloning and
overexpression experiments
of oxidases and halogenases
from natural products producing
organisms, optimizing expression
conditions and developing wholecells biotransformation systems
whilst Javier will be responsible
for setting up and developing the
in vitro assays using the purified
target enzymes.
Commenting on the project, Dr
Jesús Cortés stated “participation
in BIONEXGEN allows Entrechem to
access new technologies, knowledge
and know-how from the partners that
will lead to an increased number of our
household biocatalysts to generate
more compounds for our in-house
drug development programme and for
our biocatalysis contract service”
Dr Javier González-Sabín
A chemist by training, Javier
specialized in Biocatalysis and did
his PhD on biocatalytic synthesis of
chiral amines and amino alcohols
in Prof Vicente Gotor group at
The University of Oviedo. On
completing his PhD studies, Javier
joined Entrechem in 2005 where
he has developed biocatalytic
processes for the synthesis of
indolocarbazoles and aureolic acid
derivatives and carries out the
Company’s contract services of
biocatalytic synthesis of chiral fine
chemicals.
Dr Luz Elena Núñez
Luz Elena is a molecular biologist
specialized in genetic engineering
of biosynthetic pathways of
secondary metabolites in
Streptomyces. Luz Elena did her
PhD on cloning and engineering
of the biosynthetic pathway of
the antibiotic thienamycin in Prof
José Salas group at The University
of Oviedo. Luz Elena carried out
postdoctoral studies with Prof
Salas and Prof Juan F. Martín at
the Inbiotec (León, Spain) before
joining Entrechem in 2006. Since
then she has been involved in the
manipulation of genes responsible
for the synthesis of the main drug
candidates of the Company to
improve properties and production.
From left to right: Dr Luz Elena Núñez, Dr
Jesús Cortés, Dr Javier González-Sabín
Dr Jesús Cortés
Jesús is a chemist by training,
with a PhD in Biochemistry of
antibiotics production and worked
as a Senior Research Associate in
the Department of Biochemistry
in The University of Cambridge
(UK) for 12 years. In 2003, Jesús
moved to GSK (Stevenage, UK),
The Natural Products Research
group for 4 years before joining
Novacta Biosystems (Welwyn
Garden City, UK) where he was
involved in developing antibiotics
by manipulation of biosynthetic
pathways and developing
antibacterial evaluation protocols.
In 2010, Jesús moved to Spain to
work for Entrechem where he is
involved in manipulating the genes
involved in the synthesis of the
drug candidates of the Company
and fermentation studies for titre
improvement.
The BIONEXGEN newsletter edition 1
11
BIONEXGEN Partner Logos
Knowledge
Transfer
Network
Chemistry Innovation
This project is financially supported by the 7th Framework
Programme of the European Commission
(grant agreement number 266025)
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