Ingenza Ltd; Technologies for new catalysts and products across the industrial biotechnology spectrum
Submitting InstitutionsUniversity of St Andrews,
University of Edinburgh
Unit of AssessmentChemistry
Summary Impact TypeTechnological
Research Subject Area(s)
Chemical Sciences: Organic Chemistry, Other Chemical Sciences
Biological Sciences: Biochemistry and Cell Biology
Summary of the impact
Impact: Economic. Ingenza is a profitable SME based
in Roslin, Scotland, with 34 (12 PhD-level) staff, and a turnover of £2.7M
Significance: Ingenza Ltd is an established industrial
biotechnology (IB) and synthetic biology (SB) company which incorporated
in September 2002. Its combination of synthetic organic chemistry with
efficient methods of genetic screening, fermentation and engineered
microbial strains is used to develop competitive and scalable industrial
bioprocesses for pharma, chemicals, energy, natural product and other
Beneficiaries are Ingenza's customers (commercial and the public)
and its employees.
Research; date; attribution: In 2002 the Turner group (University
of Edinburgh, UoE) published in Angew. Chem. a new strategy of
integrated chemo- and enzymatic catalysed routes to high-value chiral
compounds that offered dramatic improvements over existing technologies
(high yield and enantiomeric excesses often > 99.9%).
Reach: Ingenza now has moved from a focus on fine chemicals to
establish long term technology development and licensing agreements with
global leading end-users in the chemicals, polymers, biofuels, food and
biologics sectors, for example in the sustainable manufacture of
poly-methylmethacrylate with Lucite International.
The Turner group in EaStCHEM developed the simultaneous use of a highly
selective oxidase biocatalyst and a chemical reducing agent or catalyst,
to prepare a huge variety of enantiopure chiral amines in high yield and
In the key paper in 2002  they demonstrated the deracemisation of the
amino acid DL-proline using commercially available D-amino acid oxidase
(DAAO) and three equivalents of NaCNBH4, a reducing agent of
sufficient water stability to be enzyme-compatible, yielding L-proline in
99% yield and 99 % ee (enantiomeric excess), achieving a 94 % conversion
of racemate to chiral amino acid after hydrolysis. Previous dynamic
kinetic resolutions have been hampered by the harsh conditions required to
racemise amines. They extended this to a range of amino acids using
commercially available oxidase enzymes.
Another key advance was the use of cloned microbial genes and the
development of in-vitro evolution of enzymes. Working in collaboration
with GSK, an enzyme from a gene maoN that oxidised simple
aliphatic amines was identified that showed a clear preference for the
oxidation of L-α-methylbenzylamine over D-α-methylbenzylamine. The group
optimised this using random mutagenesis and in vitro and in
situ selection, and colorimetric solid phase screening, to generate
new biocatalysts and commercially important targets (starting with chiral
amines) of interest to pharmaceutical industry customers.
The Turner group recognised three key points of the new method that led
them to protect the work  and then spin-out Ingenza: (i). The high
selectivity of an enzyme allows enantiomeric excesses of >99.9 %. (ii)
It converts all the potential substrate into the desired enantiomer
product, compared with a standard enzyme-catalysed kinetic resolution of a
chiral racemate. (iii). It does not require the harsh conditions required
to racemise amines that alternative transition-metal catalyst routes to
develop dynamic kinetic resolutions have.
Further UoE research to develop high throughput screening techniques 
enabled a large number of solid phase screening capabilities to address
problems faced by the biopharma industry. For example, novel screen
calibration approaches allowed the development of colorimetric oxidase
based protein fusion systems to identify the top 50 out of a
500,000-member library of candidates for a key therapeutic target.
Prof Nick Turner, EaStCHEM School of Chemistry, University of Edinburgh
10/1998-09/2004. The other co-authors are PDRAs and PhD researchers in the
Turner group, and industry collaborators. Enright was a collaborator in
Strathclyde at the time of patent filing.
Dr Ian Fotheringham, co-founder of Ingenza in 2002, now President.
Glasgow PhD, biocatalysis history with Monsanto.
Dr Robert Speight co-founder. Hired as a PDRA in 2000 to work in
Professor Turner's lab, UoE. Awarded an RSE enterprise fellowship in 2002.
References to the research
Publications: Underpinning research has been published
in international, high-quality, peer reviewed, academic journals and
receives citations from across the research area.
 * Deracemisation and stereoinversion of alpha-amino acids using D-amino
acid oxidase and hydride reducing agents. T. M. Beard, N.J. Turner, Chem.
Commun., 2002, 246-7. doi:10.1039/b107580m.
46 cits, JIF 6.4.
 Stereoinversion of β- and γ-substituted α-amino acids using a
chemo-enzymatic oxidation-reduction procedure. A. Enright, F.-R.
Alexandre, G. Roff, I.G. Fotheringham, M.J. Dawson, N.J. Turner, Chem.
Commun. 2003 2636-7. doi:
10.1039/B309787K. 18 cits, JIF 6.4.
 * Deracemization of alpha-methylbenzylamine using an enzyme obtained
by in vitro evolution. M. Alexeeva, A. Enright, M. J. Dawson, M.
Mahmoudian, N. J. Turner, Angew. Chem., Int. Ed., 2002, 41,
3177-80. doi:10.1002/1521-3773(20020902)41:17<3177::AID-ANIE3177>3.0.CO;2-P/abstract.74cits, JIF 13.7.
 Identification of broad specificity P450(CAM) variants by primary
screening against indole as substrate. A. Celik, R.E. Speight, N.J.
Turner, Chem. Commun. 2005, 3652-54. doi:10.1039/B506156C.
18 cits, JIF 6.4.
 * Chemo-Enzymatic Synthesis of Unnatural Amino Acids in
Asymmetric Synthesis and Application of α-Amino Acids. I. V. Archer, S. A.
Arnold, R. Carr, I. V. Fotheringham, R. E. Speight, P. P. Taylor. ACS
Symposium series. 2009, Vol. 1009, ch 20, p. 322-336.ISBN13:
9780841269743 eISBN: 9780841224841 Eds. V. A. Soloshonok and K.
Izawa. [peer-reviewed book chapter] http://pubs.acs.org/doi/abs/10.1021/bk-2009-1009.ch020.
 Patent with GSK (industrial collaborators at the time) M. V.
Alexeeva, A. Enright, N. J. Turner, M. Mahmoudian, R. M. Thornley
(WO.2003.080855.A2, GB0206415.2, filed 19 March 2002); `enzymatic
deracemisation of amines'.
Dec 2001: Ligand discovery at Edinburgh University funded by Cyclacel (UK
industry) (£702,360). Jan 2002: Development of enantioselective amine
oxidases for application in the deracemisation of racemic chiral amines,
July 2009: SMART R&D: A new scalable biocatalytic technology to
produce enantiomerically pure Unnatural Amino Acids (£475,108).
July 2010: To develop an improved bedside diagnostic (£69,747).
Nov 2010: Two Biosciences KTN SPARK Awards: Improved fed-batch
fermentation protocols and Genome sequencing of improved yeast for biofuel
applications (£5k each).
March 2011: TSB 100970 (with Edinburgh and Aberdeen Universities): Mining
new enzymes in the rumen for biomass processing and chiral synthesis
August 2011: TSB 100962 (with Edinburgh University). Adapted yeast for
superior carbon conversion (£578,890).
Details of the impact
Ingenza is an industrial biotech company spun out from EaStCHEM research,
which employs 34 people and had a turnover last year of £2.7M. [F1] It is
based in Roslin BioCentre, a science park in Midlothian for
research-intensive and commercial life-science related SMEs. Ingenza was
set up to optimise and exploit the new robust, general, and scalable
biocatalysis platform technology described above. The new screening
methods for strain-engineering developed in the research has helped the
company expand its portfolio of biocatalysed transformations and
engineered production microbes into other industry sectors, with
wide-ranging catalysed transformations for polymers, biofuels, feedstocks,
nutrition and other applications. These enabling technologies have helped
establish Ingenza as the leading UK industrial biotechnology and synthetic
biology company. As a direct result, Ingenza's staff has grown 2-fold in
the past 4 years and revenues have grown 5-fold. The President of Ingenza,
in a corroborating letter, states " Turner's group conducted important
research at the School of Chemistry between 2001 and 2003...This work
was an important foundation on which we originally built Ingenza's
business base...Since that time Ingenza has evolved and diversified into
the leading industrial biotechnology and synthetic biology company in
the UK with global reach in its customer base and technology
implementation...I can attest to direct linkage between research ...and
the significant societal and economic impacts that followed the spinning
out of Ingenza and its ongoing expansion" [F1]. The Life Sciences
Director at Scottish Enterprise said "The company ... is a great
example of Scotland's thriving life sciences sector" [S2].
In the financial year 2012-2013 Ingenza turned over £2.7M and expects to
continue strong and profitable growth as its capabilities and interface
with multiple market sectors expand. Ingenza's revenue growth reflects the
unique capabilities of the company's technology in a challenging economic
climate and its adaptability to other industries' awareness and uptake of
sustainable manufacturing practices. Total turnover for 2008-July 2013 =
a. Development of bioprocess routes to pharmaceuticals/chemical
building blocks Industrial biotechnology as a means to produce
platform chemicals, polymer or important drug intermediates is of high and
increasing value. Enzyme expertise (engineering and catalysis optimisation
by directed evolution) has been applied to the large-scale manufacture of
pharmaceutical intermediates. The value of sales for 2008-July 2013 is
b. Provision of process development and bioprocess optimisation for
other industries The enabling technologies developed in Section 2
are being used much more broadly by Ingenza for bioprocess optimisation
and supply of improved production microbes, to provide large industries
with new, sustainable manufacturing processes from renewable rather than
petrochemical feedstocks. For example, multi-year partnerships have been
established with leading global companies, such as Lucite International,
the world's leading manufacturer of poly-methylmethacrylate [S3]. Ingenza
piloted one of its improved biofuel strains with another end-user in the
US at full production scale of 2.4 million litres; the Ingenza President
can provide information on the number and range of other companies that
have benefitted. A major two-year development programme employing five
people at Ingenza to work with Invista, one of the world's largest
integrated producers of polymers and fibres (10,000 employees in 20
countries), has also just completed successfully, with ten people starting
on this project in the near future as a result of the expansion of the
project. The Ingenza President can provide corroboration on this [F1]. The
President of Invista is quoted in the most recent press announcement "We
see Ingenza's capabilities as very complementary to our own and are
pleased to announce this extended collaboration." [S4]
In a corroborating letter, the co-founder of Ingenza, who recently moved
to Australia to be involved in new biotechnology start-up initiatives
writes "The deracemisation research and the interest that was
generated by the high impact publications in Nick Turner's group was
really the foundation of Ingenza ... and the interest that was generated
by the high impact publications. As well as the research, the School of
Chemistry really supported Ingenza in those first few years in an
operational sense and that support was key to starting the company on a
strong footing...The ongoing relationship with the School of Chemistry
has also been important for Ingenza... The international impact of the
published research from Prof Turner's lab meant that Ingenza had a
standing on the world stage from day one to the present day, with the
majority of company's business coming from abroad." [F2]
Ingenza's scientific team spans the disciplines of molecular biology,
biochemistry, enzymology, fermentation science and synthetic organic
chemistry, and has recruited and trained numerous scientists, including 12
scientists trained to PhD or post-doctoral level at Edinburgh University.
Currently 34 staff are employed, 12 of whom have PhDs.[F1]
There is also strong R+D collaboration with EaStCHEM staff, with joint
awards from TSB, SPARK, ERA-NET, and collaborative PhD students. Ingenza
has engaged with the Government's Modern apprentice scheme since 2009,
winning 'Small Employer of the Year 2011' at the Scottish Modern
Apprenticeship Awards.[S4] In 2012 Scottish Minister for Youth Employment,
said "I commend Ingenza for their forward thinking approach in
fostering a new generation of young scientists, and offering up some
excellent opportunities for training in this exciting sector".[S5]
Impact Development Timeline:
2002 First paper and patent; Ingenza launched and incubated within
School of Chemistry.[F1]
2003 The Edinburgh (University) technology fund invested £25,000
in Ingenza for a 5% stake; Ingenza won £120,000 funding from the Scottish
Executive, Scottish Enterprise and the Royal Society of Edinburgh.
2005 Scottish Enterprise helped Ingenza with direct funding
(£20,000) to offset costs of new business development. This helped Ingenza
to establish its initial base of customers and strategic partners.
2007 Commercialisation partnership established with Richmond
2008-2010 Awarded 2 new SMART awards and 3 Technology Strategy
Board grant awards, two in partnership with the University of Edinburgh,
totalling in excess of £1M. Receives two Biosciences KTN SPARK Awards.
2011 1) A multi-year bioprocess development agreement is signed
with Lucite International for bio-manufactured monomers.[S3] 2) Awarded
over £500k from TSB for three new biotechnology projects on Industrial
Biotechnology and the commercial application of high-throughput genome
sequencing, demonstrating Ingenza's diversity and leading position in
industrial biotechnology. 3) Ingenza named 'Small Employer of the Year
2011'[S4] for its technical apprenticeship scheme. 4) 5 people at Ingenza
are employed to work on a large bioprocess development project for
2012 1) Opening of a new GMP compatible clean room with additional
local council investment of £50,000.[S6] 2) Ingenza is featured case study
in Scottish Parliament Life Sciences event.[S7]
2013 Currently 34 staff employed [F1], Current turnover in excess
of £2.7 M.
Sources to corroborate the impact
[F1] Letter corroborating the link between EaStCHEM research and Ingenza;
President of Ingenza. Can be contacted to corroborate staff numbers,
turnover and sales
[S1] Scottish Enterprise support for Ingenza, http://news.ingenza.com/?p=354,
includes a quote from their Life Sciences Director
[S2] 2011 Ingenza and Lucite International in multi-year bioprocess
[F2] Corroborating support letter from the co-founder of Ingenza [now
Business Manager, Australian Institute for Bioengineering and
[S3] Press release from Invista Intermediates — extension of
collaboration set up before July 2013 (includes quote from company
[S4] 2011 Small Employer of the Year (Skills Development Scotland)
[S5] Visit to Ingenza from Scottish Minister for Youth Employment http://news.ingenza.com/?p=377
[S6] 2012 Ingenza new clean room with council investment:
[S7] Scottish Parliament -Life Sciences event http://www.lsscommunity.com/profiles/blogs/life-sciences-scotland-exhibition-at-the-scottish-parliament.