Synthetic Biology UK 2015 675 rsity of , ¶ reative Commons Attribution License , Philip Shapira* 1  sectors.a SYNBIOCHEM long-term also visionof builds and Manchester on commitmentleveraging in and by integrating world-leading sustainable capabilities theCentres in of MIB Industrial University Excellence including: , Biotechnology, Biotransform- ation and Biocatalytic Manufacture (CoEBio3);Centre Manchester for andCentre Catalysis for (MCBC); Integrative Manchester Michael Systems Biology Barber (MCISB) CollaborativeSYNBIOCHEM and Centre was the established for in MS 2014the funded U.K. (MBCMS). jointly Biotechnology by Council, and Biological the SciencesResearch Research U.K. Council and Engineering Theby three University and directors of (Nigel Manchester. PhysicalTurner) Scrutton, Led the Eriko Centre Takano Sciences unites and a Nick researchers complementary team at of Manchester SynBio that in will pursuit of delivermore SynBio wider rapid solutions access andfor scalable to production/manufacturing. predictable The chemical interdisciplinary deliveryteam diversity of includes and chemical not onlyscientists, targets but also chemists, investigators from the biologists Manchester Institute andof computer Innovation Research andcontributing insight of the RRI relevant to School the Centre activities. of A Social Sciences  , Jason Micklefield*†, Nigel S. Scrutton*† § and Nicholas J. Turner*†  MIB, Manchester Institute of Biotechnology; RRI, Responsible Research and Abstract The Manchester Synthetic Biologysustainable production Research of fine Centre and speciality chemicals. (SYNBIOCHEM) Thea Centre’s is unique integrated technology capability a platforms to provide foundry facilitate predictableAn for engineering overview the of of microbial these biosynthesis bio-factories capabilities and for is chemicals described. production. biocatalysis, fine chemicals, metabolic engineering, synthetic biology, systems

SYNBIOCHEM is located in the Manchester Institute of 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the C To whom correspondence should be addressed (email nigel.scrutton@manchester. SYNBIOCHEM Responsible Research Innovation Lead, Alliance Manchester Business School, The , Manchester, U.K. SYNBIOCHEM Platform/Theme Lead, School of Chemistry,SYNBIOCHEM The Data University Lead, of School Manchester, of Manchester, Computer U.K. Science, The University of Manchester, Manchester, U.K. SYNBIOCHEM, The University of Manchester, Manchester, U.K. SYNBIOCHEM, Manchester Institute of Biotechnology, The University of Manchester, Manchester, U.K. c Biochem. Soc. Trans. (2016) 44, 675–677; doi:10.1042/BST20160009 1 Key words: biology. Abbreviations: Innovation; SynBio, Synthetic Biology. Biotechnology (MIB; http://www.mib.ac.uk/) and builds on the MIB’s core strategy of unitingscientists teams of and interdisciplinary industrialinnovation partners in to bio-based deliver chemicals and challenge-led broader industrial The Manchester UniversityCentre Synthetic (SBRC), Biologyco.uk), is Research focused SYNBIOCHEM on deliveringsolutions that Synthetic provide innovative, (http://synbiochem. Biology fast, (SynBio) predictable and robust production routes for diverseunderpinned by fine Responsible Research and and Innovation speciality (RRI). chemicals By harnessing theSYNBIOCHEM power is ofmanufacturing predictive driving processes SynBio that methods, next-generation arecially appropriate relevant and sustainable commer- for(e.g. scale-up across healthcare, manypharmaceuticals, industrial energy, novel materials sectors agrichemicals, and bioremediation). green chemistry, 4.0 (CC BY).

*BBSRC/EPSRC Synthetic Biology Research Centre for Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, The Unive

and speciality chemicals Pablo Carbonell*, Andrew Currin*, MarkChristopher Dunstan*, J. Donal Robinson*, Fellows*, Neil Adrian Swainston*, Jervis*,Rainer Maria Nicholas Breitling*†, Vinaixa*, J.W. George Alan Rattray*, Guo-Qiang Williams*, Chen*†, CunyuDouglas Jean-Loup Yan*, B. Faulon*†, Perdita Kell*†, Carole Barran*†, Rosalind Goble*‡, Le Royston Feuvre* Goodacre*†, biosynthesis and sustainable production of fine Manchester, Manchester, U.K. † ‡ §  ¶ SYNBIOCHEM – a SynBio foundry for the Synthetic Biology UK 2015 ac.uk). Eriko Takano*† 676 Biochemical Society Transactions (2016), Volume 44, part 3

Figure 1 Schematic of the SYNBIOCHEM synthetic biology foundry Schematic of the foundry concept established in SYNBIOCHEM that enables iterative Design, Build and Test workflows for the engineering of new biological parts (e.g. and regulatory components), devices (e.g. pathways and cellular compartments) and systems (microbial chassis and processes).

key challenge includes consideration of the societal impact of which are currently focused on the engineering of microbial SYNBIOCHEM research activities to ensure that the Centre bio-factories for the sustainable production, scale-up and anticipates, prepares for and, if necessary, mitigates the impact diversification of terpenoids, flavonoids and alkaloids. of SynBio technology in the wider society, economy and SYNBIOCHEM has an open and collaborative culture environment [1]. with a strong emphasis on building academic and industry SYNBIOCHEM has established state-of-the-art and fully partnerships, both at the national and international levels. integrated Design/Build/Test technology platforms for bio- Industrial foresight and awareness coupled to translation of based chemicals production (Figure 1). The platforms SYNBIOCHEM discovery science and technology towards include innovative DESIGN platforms for the computational commercial exploitation are at the core of the Centre’s modelling and design of biological parts, devices and strategy. The Centre hosts regular open meetings in a variety chassis; state-of-the-art high-throughput and automated of formats, enabling one-to-one discussions with industrial BUILD capabilities for the rapid assembly of engineered partners, the development of new collaborative projects with microbial systems; and a suite of advanced analytical TEST external stakeholders, and through an industry club for joint technologies, including mass spectrometers for sensitive supervision of research studentships in projects that address targeted chemical detection and untargeted metabolomics, scientific problems of interest to the club members. Early and picodroplet/fermentation platforms for production and SYNBIOCHEM programmes have resulted in protection analysis from the single cell through to the 1 l scale. The of new intellectual property for the development of tools technology platforms are supported by a comprehensive and microbial factories/hosts relevant to the production fully shared standards-compliant data management platform of pravastatin [2], biosynthetic menthol [3] and propane that ranges from laboratory information management system [4], the development of new regulatory components (e.g. (LIMS) to notebooks to cross project cataloguing that riboswitches [5]) and the discovery of new biocatalysts for will be openly available. The SYNBIOCHEM platforms chemicals production that provide new routes to alkenes are supported by an expert team of Senior Experimental [6,7] and enantiopure amines [8]. This is supported by unique Officers to implement the Centre’s science programmes, technology innovations in DNA design and assembly [9,10]

c 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Synthetic Biology UK 2015 677

that underpin the rapid construction and evolution of new 4Menon,N.,P´asztor, A., Menon, B.R.K., Kallio, P., Fisher, K., Akhtar, M.K., parts and pathways through, for example new approaches to Leys, D., Jones, P.R. and Scrutton, N.S. (2015) A microbial platform for renewable propane synthesis based on a fermentative butanol pathway. [11]. Many of these discoveries are subject Biotechnol. Biofuels 8,61CrossRef to new SYNBIOCHEM patent submissions and, in one case, 5 Wu, M.C., Lowe, P.T., Robinson, C.J., Vincent, H.A., Dixon, N., Leigh, J. and have already supported the formation of an early spinout Micklefield, J. (2015) Rational re-engineering of a transcriptional company from the Centre. silencing PreQ1 riboswitch. J. Am. Chem. Soc. 137, 9015–9021 CrossRef In summary, SYNBIOCHEM is addressing major chal- 6 Payne, K.A., White, M.D., Fisher, K., Khara, B., Bailey, S.S., Parker, D., lenges in SynBio through a foundry concept and an open Rattray, N.J., Trivedi, D.K., Goodacre, R., Beveridge, R. et al. (2015) New collaborative ethos with external partners. The Centre’s supports α,β-unsaturated acid decarboxylation via 1,3-dipolar integrated technology platforms provide a unique capability cycloaddition. 522, 497–501 CrossRef 7 White, M.D., Payne, K.A., Fisher, K., Marshall, S.A., Parker, D., Rattray, to facilitate predictable engineering of microbial bio-factories N.J., Trivedi, D.K., Goodacre, R., Rigby, S.E., Scrutton, N.S. et al. (2015) for chemicals production. Further information about the UbiX is a flavin prenyltransferase required for bacterial ubiquinone Centre and routes to collaboration can be obtained from the biosynthesis. Nature 522, 502–506 CrossRef SYNBIOCHEM website: http://synbiochem.co.uk. 8 Mutti, F.G., Knauss, T., Scrutton, N.S., Breuer, M. and Turner, N.J. (2015) Conversion of alcohols to enantiopure amines through dual– hydrogen-borrowing cascades. Science 349, 1525–1529 CrossRef 9 Currin, A., Swainston, N., Day, P.J. and Kell, D.B. (2014) SpeedyGenes: an References improved gene synthesis method for the efficient production of 1 Li, Y. and Shapira, P. (2016) Synthetic biology: reshaping the future? error-corrected, synthetic protein libraries for directed evolution. Protein PLOS Synbio. Blog., https://t.co/v91JxkPFWf Eng. Des. Sel. 27, 273–280 CrossRef 2 McLean, K.J., Hans, M., Meijrink, B., van Scheppingen, W.B., Vollebregt, 10 Currin, A., Swainston, N., Day, P.J. and Kell, D.B. (2014) GeneGenie: A., Tee, K.L., van der Laan, J.M., Leys, D., Munro, A.W. and van den Berg, optimized oligomer design for directed evolution. Nucleic Acids Res. 42, M.A. (2015) Single-step fermentative production of the W395–W400 CrossRef cholesterol-lowering drug pravastatin via reprogramming of Penicillium 11 Currin, A., Swainston, N., Day, P.J. and Kell, D.B. (2015) Synthetic biology chrysogenum. Proc. Natl. Acad. Sci. U.S.A. 112, 2847–2852 CrossRef for the directed evolution of protein biocatalysts: navigating sequence 3 Toogood, H.S., Cheallaigh, A.N., Tait, S., Mansell, D.J., Jervis, A., Lygidakis, space intelligently. Chem. Soc. Rev. 44, 1172–1239 CrossRef A., Humphreys, L., Takano, E., Gardiner, J.M. and Scrutton, N.S. (2015) Enzymatic menthol production: one-pot approach using engineered Received 15 January 2016 Escherichia coli. ACS Synth. Biol. 4, 1112–1123 CrossRef doi:10.1042/BST20160009

c 2016 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).