Synlett 2013; 24(2): 150-156
DOI: 10.1055/s-0032-1317498
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© Georg Thieme Verlag Stuttgart · New York

From Commercial Enzymes to Biocatalysts Designed by Protein Engineering

Uwe T. Bornscheuer*
Department of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany   Fax: +49(3834)86794367   Email: uwe.bornscheuer@uni-greifswald.de
› Author Affiliations
Further Information

Publication History

Received: 24 August 2012

Accepted after revision: 01 October 2012

Publication Date:
09 November 2012 (online)


Abstract

This account provides a personal view on the development of biocatalysis over the last two decades. Examples include the use of commercial enzymes, such as lipases, (recombinant) esterases, transaminases, and Baeyer–Villiger monooxygenases for the synthesis of optically pure compounds. The opportunity provided by modern protein engineering methods to tailor design an enzyme for a given scientific problem (substrate scope, selectivity, stability) is emphasized together with concepts to boost this technology in terms of timelines and success.

1 Introduction

2 Unexpected Discoveries

2.1 To Protect and Serve

2.2 ‘Abnormal’ Access to β-Amino Acids

3 Defined Enzyme Is Better Than Crude Extract

4 New Horizons Opened by Protein Engineering

4.1 Random Mutagenesis Can Give Random Results

5 Exploring Sequence and Structure Databases

5.1 Massive Alignment Identifies Evolutionary Variations

5.2 Fixing Wrong Annotations Can Yield a Toolbox of Novel Enzymes

6 Conclusion

 
  • References

  • 1 Bornscheuer UT, Huisman GW, Kazlauskas RJ, Lutz S, Moore JC, Robins K. Nature (London) 2012; 485: 185
  • 2 Rosenthaler L. Biochem. Z. 1908; 14: 238
  • 3 Buchholz K, Kasche V, Bornscheuer UT. Biocatalysts and Enzyme Technology . 2nd ed Wiley-VCH; Weinheim: 2012
  • 4 Zaks A, Klibanov AM. Science (Washington, DC, U.S.) 1984; 224: 1249
  • 5 Bornscheuer UT, Kazlauskas RJ. Hydrolases in Organic Synthesis – Regio- and Stereoselective Biotransformations. Wiley-VCH; Weinheim: 2005
    • 6a Industrial Biotransformations . Liese A, Seelbach K, Wandrey C. Wiley-VCH; Weinheim: 2006
    • 6b Breuer M, Ditrich K, Habicher T, Hauer B, Keßeler M, Stürmer R, Zelinski T. Angew. Chem. Int. Ed. 2004; 43: 788
  • 7 Kazlauskas RJ, Weissfloch AN. E, Rappaport AT, Cuccia LA. J. Org. Chem. 1991; 56: 2656
  • 8 Weissfloch AN. E, Kazlauskas RJ. J. Org. Chem. 1995; 60: 6959
  • 9 Lampe TF. J, Hoffmann HM. R, Bornscheuer UT. Tetrahedron: Asymmetry 1996; 7: 2889
  • 10 Höhne M, Robins K, Bornscheuer UT. Adv. Synth. Catal. 2008; 350: 807
    • 11a Balke K, Kadow M, Mallin H, Sass S, Bornscheuer UT. Org. Biomol. Chem. 2012; 10: 6249
    • 11b Rehdorf J, Bornscheuer UT. Monooxygenases, Baeyer–Villiger Oxidations in Organic Synthesis. In Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology. Flickinger MC. John Wiley & Sons; Hoboken, NJ: 2010. DOI: 10.1002/9780470054581.eib451
    • 12a Kirschner A, Bornscheuer UT. Angew. Chem. Int. Ed. 2006; 45: 7004
    • 12b Rehdorf J, Mihovilovic MD, Bornscheuer UT. Angew. Chem. Int. Ed. 2006; 45: 4506
    • 13a Tamm C. Pure Appl. Chem. 1992; 64: 1187
    • 13b Zhu L.-M, Tedford MC. Tetrahedron 1990; 46: 6587
    • 14a Heymann E, Junge W. Eur. J. Biochem. 1979; 95: 509
    • 14b Junge W, Heymann E. Eur. J. Biochem. 1979; 95: 519
  • 15 Seebach D, Eberle M. Chimia 1986; 40: 315
  • 16 Musidlowska A, Lange S, Bornscheuer UT. Angew. Chem. Int. Ed. 2001; 40: 2851
  • 17 Hummel A, Brüsehaber E, Böttcher D, Trauthwein H, Doderer K, Bornscheuer UT. Angew. Chem. Int. Ed. 2007; 46: 8492
  • 18 Lange S, Musidlowska A, Schmidt-Dannert C, Schmitt J, Bornscheuer UT. ChemBioChem 2001; 2: 576
  • 19 Böttcher D, Brüsehaber E, Doderer K, Bornscheuer UT. Appl. Microbiol. Biotechnol. 2007; 73: 1282
  • 20 Hermann M, Kietzmann MU, Ivancic M, Zenzmaier C, Luiten RG, Skranc W, Wubbolts M, Winkler M, Birner-Gruenberger R, Pichler H, Schwab H. J. Biotechnol. 2008; 133: 301
  • 21 Moore JC, Arnold FH. Nat. Biotechnol. 1996; 14: 458
  • 22 Stemmer WP. C. Nature (London) 1994; 370: 389
  • 23 Bornscheuer UT, Altenbuchner J, Meyer HH. Biotechnol. Bioeng. 1998; 58: 554
    • 24a Henke E, Bornscheuer UT, Schmid RD, Pleiss J. ChemBioChem 2003; 4: 485
    • 24b Henke E, Pleiss J, Bornscheuer UT. Angew. Chem. Int. Ed. 2002; 41: 3211

      For reviews, see:
    • 25a Kourist R, Bornscheuer UT. Appl. Microbiol. Biotechnol. 2011; 91: 505
    • 25b Kourist R, Dominguez de Maria P, Bornscheuer UT. ChemBioChem 2008; 9: 491
  • 26 Baumann M, Hauer BH, Bornscheuer UT. Tetrahedron: Asymmetry 2000; 11: 4781
  • 27 Baumann M, Stürmer R, Bornscheuer UT. Angew. Chem. Int. Ed. 2001; 40: 4201
  • 28 Schmidt M, Hasenpusch D, Kähler M, Kirchner U, Wiggenhorn K, Langel W, Bornscheuer UT. ChemBioChem 2006; 7: 805
  • 29 Lorenz P, Eck J. Nature Rev. Microbiol. 2005; 3: 510
    • 30a Reetz MT, Wang LW, Bocola M. Angew. Chem. Int. Ed. 2006; 45: 1236
    • 30b Behrens GA, Hummel A, Padhi SK, Schätzle S, Bornscheuer UT. Adv. Synth. Catal. 2011; 353: 2191
  • 31 Reetz MT. Angew. Chem. Int. Ed. 2011; 50: 138
    • 32a Kourist R, Jochens H, Bartsch S, Kuipers R, Padhi SK, Gall M, Böttcher D, Joosten HJ, Bornscheuer UT. ChemBioChem 2010; 11: 1635
    • 32b Kuipers RK, Joosten H.-J, van Berkel WJ. H, Leferink NG. H, Rooijen E, Ittmann E, van Zimmeren F, Jochens H, Bornscheuer U, Vriend G, Martins dosSantos V. A. P, Schaap PJ. Proteins Struct. Funct. Bioinf. 2010; 78: 2101
  • 33 Jochens H, Bornscheuer UT. ChemBioChem 2010; 11: 1861
  • 34 Jochens H, Aerts D, Bornscheuer UT. Protein Eng. Des. Sel. 2010; 23: 903
  • 35 Höhne M, Schätzle S, Jochens H, Robins K, Bornscheuer UT. Nat. Chem. Biol. 2010; 6: 807
  • 36 Schätzle S, Steffen-Munsberg F, Thontowi A, Höhne M, Robins K, Bornscheuer UT. Adv. Synth. Catal. 2011; 353: 2439