Abstract
Enzymes are the subset of proteins that catalyse the chemistry of life, transforming both macromolecular substrates and small molecules. The precise three-dimensional architecture of enzymes permits almost unerring selectivity in physical and chemical steps to impose remarkable rate accelerations and specificity in product-determining reactions. Many enzymes are members of families that carry out related chemical transformations and offer opportunities for directed in vitro evolution, to tailor catalytic properties to particular functions.
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References
Peiser, G. et al. Formation of cyanide from carbon 1 of 1-aminocyclopropane-1-carboxylic acid during its conversion to ethylene. Proc. Natl Acad. Sci. USA 81, 3059–3063 ( 1984).
Sancar, A. Structure and function of DNA photolyase. Biochemistry 33, 2–9 (1994).
Schofield, C. J. et al. Proteins of the penicillin biosynthesis pathway. Curr. Opin. Struct. Biol. 7, 857–864 (1997).
Bertino, I., Gray, H. B., Lippard, S. J. & Valentine, J. S. Bioinorganic Chemistry (University Science Books, Mill Valley, CA, 1994).
Gesteland, R., Atkins, J. & Cech, T. R. (eds) The RNA World 2nd edn (Cold Spring Harbor Laboratory Press, 1999).
Narlikar, G. J. & Herschlag, D. Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes. Annu. Rev. Biochem. 66, 19– 59 (1997).
Sheppard, T. L., Ordoukhanian, P. & Joyce, G. F. A DNA enzyme with N-glycosylase activity. Proc. Natl Acad. Sci. 97, 7802–7807 (2000).
Zhang, B. & Cech, T. R. Peptide bond formation by in vitro selected ribozyme. Nature 390, 96–100 (1997).
Cech, T. R. & Golden, B. L. in The RNA World 2nd edn (eds Gesteland, R., Atkins, J. & Cech, T. R.) 321– 349 (Cold Spring Harbor Laboratory Press, 1999).
Radzicka, A. & Wolfenden, R. A proficient enzyme. Science 267, 90–93 ( 1995).
Stryer, L. Biochemistry 4th edn (Freeman, San Francisco, 1995).
Patten, P. A. et al. The immunological evolution of catalysis. Science 271, 1086–1091 ( 1996).
Wagner, J. A., Lerrner, R. A. & Barbas, C. F. III Efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes. Science 270, 1797–1800 (1995).
Smithrud, D. B. & Benkovic, S. J. The state of antibody catalysis. Curr. Opin. Biotechnol. 8, 459–466 (1997).
Lippard, S. J. & Berg, J. M. Principles of Bioinorganic Chemistry (University Science Books, Mill Valley, CA, 1994).
Walsh, C. T. & Orme-Johnson, W. H. Nickel enzymes. Biochemistry 26, 4901–4906 (1987).
Watt, R. K. & Ludden, P. W. Nickel binding proteins. Cell Mol. Life Sci. 56, 604–625 (1999).
Wong, C.-H. & Whitesides, G. M. Enzymes in Synthetic Organic Chemistry (Pergamon, Oxford, 1994).
Cane, D. (ed.) Thematic issue on polyketide and nonribosomal peptide synthases. Chem. Rev. 97, 2463–2705 (1997).
Konz, D. & Marahiel, M. How do peptide synthetases generate structural diversity? Chem. Biol. 6, R34 –R38 (1999).
Cane, D. E., Walsh, C. T. & Khosla, C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282, 63– 68 (1998).
Trauger, J., Kohli, R. M., Mootz, H., Marahiel, M. & Walsh, C. Peptide cyclization catalysed by the thioesterase domain of tyrocidine synthetase. Nature 407, 215 –218 (2000).
Roach, P. L. et al. The crystal structure of isopenicillin N synthase, first of a new structural family of enzymes. Nature 375, 700–704 (1995).
Valegard, K. et al. Structure of a cephalosporin synthase. Nature 394, 805–809 (1998).
Que, L. One motif—many different reactions. Nature Struct. Biol. 7, 182–184 (2000).
SinhaRoy, R., Milne, J., Belshaw, P., Gehring, A. & Walsh, C. Oxazole and thiazole peptide biosynthesis. Nat. Prod. Rep. 16, 249–263 (1999).
Lewis, R. et al. Molecular mechanisms of drug inhibition of DNA gyrase. BioEssays 18, 661–671 ( 1996).
Quadri, L. E., Keating, T. A., Patel, H. M. & Walsh, C. Assembly of the Pseudomonas aeruginosa nonribosomal peptide siderophore pyochelin: in vitro reconstitution of aryl-2,4-bis-thiazoline synthetase activity from PchD, E and F. Biochemistry 38, 14941 –14954 (1999).
Gehring, A., Mori, I., Perry, R. & Walsh, C. The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of Yersinia pestis. Biochemistry 37, 11637–11650 (1998).
Babbit, P. C. et al. The enolase superfamily: a general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids. Biochemistry 35, 16489–16501 ( 1996).
Gerlt, J. A. & Babbit, P. C. Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis. Curr. Opin. Chem. Biol. 2, 607–612 (1998).
Hubbard, B. K. Functional and mechanistic investigations of enzymes in the enolase superfamily . Thesis, Univ. Illinois (2000)
Tobin, M. B., Gustafsson, C. & Huisman, G. W. Directed evolution: the rational basis for irrational design. Curr. Opin. Struct. Biol. 10, 421 –427 (2000).
Schmidt-Dannert, C., Umeno, D. & Arnold, F. Molecular breeding of carotenoid biosynthetic pathways . Nature Biotechnol. 18, 750– 753 (2000).
Madison, L. L. & Huisman, G. J. Metabolic engineering of poly(3-hydroxyalkanoates): from DNA to plastic. Microbiol. Mol. Biol. Rev. 63, 21–53 ( 1999).
Wackett, L. P. et al. Predicting microbial degradation pathways. Am. Soc. Microbiol. News 65, 87–94 (1999).
McDaniel, R., Ebert-Khosla, S., Hopwood, D. A. & Khosla, C. Rational design of aromatic polyketide products by recombinant assembly of enzymatic subunits. Nature 375, 549– 554 (1995).
Bizily, S. P., Rugh, C. L., Summers, A. O. & Meagher, R. B. Phytoremediation of methylmercury pollution: merB expression in Arabidopsis thaliana confers resistance to organomercurials. Proc. Natl Acad. Sci. USA 96, 6808– 6813 (1999).
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Walsh, C. Enabling the chemistry of life. Nature 409, 226–231 (2001). https://doi.org/10.1038/35051697
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DOI: https://doi.org/10.1038/35051697
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