Sustainable industrial processes based on a C C bond- forming enzyme planorm

Transcription

1 Maximizing the Impact of KET Biotechnology, EC-Workshop Brussels 2016 Sustainable industrial processes based on a C C bond- forming enzyme planorm Wolf- Dieter Fessner/TUDA Simon Charnock/PRZ This project has received funding from the European Union s Horizon 2020 Research and Innova>on Programme under Grant Agreement No

2 C- C Bond Forma>on in Pharma Patents Evolution of C C bond formation over time cross coupling chemistry mostly Pd catalysis boronic acids, stannanes J. Med. Chem. 2016, 59,

3 Palladium Mining Norilsk Norilsk has largest known Ni-Cu-Pd deposits in the world. Norilsk is one of the 10 most polluted places on Earth. 1% of global S 2 emissions are from Norilsk's Ni mines. Estimated 4,000,000 tons of Cd, Cu, Pd, Ni, As, Se, and Zn are released into the air every year. 3

4 C- C Bond Forma>on by Palladium Catalysis The toolkit for C C bond formations looks much different from 40 years ago: In 2015 the preferred types are Suzuki, Sonogashira, Stille [...] reaction [...]. The Pd-catalyzed reactions are highly selective, mechanistically well-understood and operationally easy to run. n the contrary, in 1976 the most used reaction types were Wittig olefination, Grignard, Barbier, Friedel Crafts acylation, Mannich, Horner Wadsworth Emmons, aldol and Knoevenagel condensation. All of these depend upon modifying the reactivity of a carbonyl group to form the new C C bond: most use strong bases (pk a > 20) or strong Lewis acids (AlCl 3, BF 3 ) as promoters. reaction types preferred by Nature mild conditions due to enzyme catalysis no strong base needed no strong acid needed 4

5 C- C Bond Forma>on by Enzyme Catalysis Nature s toolkit for C C bond formations offers multiple opportunities + S. cerevisiae C 2 H C 2 H (R)-PAC Ephedrin H 2 C H C 2 H N H C 2 H + aldolase C 2 H N H monatin precursor Cl + DERA Cl H H Cl H H statin precursor 5

6 CarbaZymes Project construction and use of innovative, competitive platform technologies development of cutting-edge biotechnology as future innovation driver widening industrial application of enzymatic processes 6

7 CarbaZymes Impact: Enzymes ALD (024) enzyme panel construction: from hits to homologs 7

8 CarbaZymes Impact: Bioinforma>cs 3DM Protein Super- family Informa>on Systems Structures Alignments Literature All the data is connected 8

9 Mul>- scale Enzyme Produc>on How to produce 1000 novel enzymes!!! 9

10 CarbaZymes Impact: Innova>on Science Technology Process Market Research Development Demo Market IP know-how Product Return Milestones achieved mid-term status large-scale bioprospecting (>500 novel aldolases) 3DM superfamily databases constructed for enzymes of interest focused libraries constructed for enzyme optimization thermostable variants of enzymes of interest found and characterized mutability landscapes constructed for activity, chemo-, solvent, thermostability supercompetent Thermus strain constructed biocatalytic process development for scale-up transfer in progress for new developments into operational environments 1 patent application filed (pending) 2 patent applications in preparation several spin-offs: new chiral building blocks for future applications 10

11 CarbaZymes Impact: Educa>on / Training CarbaZymes makes use for dissemination, and profits from cross-fertilization with the scientific community, based on overlapping interests with the EU-funded network of the CST Action CM1303 Systems Biocatalysis CarbaZymes will co-organize the major conference series BioTrans 2017 / 2019 CarbaZymes will organize the conference sequel of Novel Enzymes

12 CarbaZymes Impact: Environment Biocatalytic processes can offer extensive advantages over traditional chemistry regarding the environmental impact In particular, enzyme-catalyzed carboligations developed in CarbaZymes will result in: reduction of toxic reagents, metal catalysts reduction of organic solvents used reduced energy consumption reduction of waste generated reduced C 2 release into the atmosphere Biotechnology-based industrial processes based on CarbaZymes technology will drive both sustainability and global competitiveness 12

13 CarbaZymes Impact: Chemical Industry CarbaZymes will provide relevant case studies for bringing Industrial Biotechnology from research lab to market, to solve the bottle-necks in industrial valorisation Demonstration of the power of enzymatic C C bond formation for the manufacture of bulk chemicals and large volume specialty chemicals, e.g.: Precursors for bulk polymers Intermediates for APIs New-to-market fine chemicals and chiral building blocks CarbaZymes development of new industry-ready carboligation enzymes will have a major impact on the biotechnology sector due to the partnership with Evonik, one of the world s leading specialty chemicals companies, together with other biotech SMEs 13

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15 Thank you for your a^en>on! CarbaZymes mo18 15