Substrate recognition by the multifunctional cytochrome P450 MycG in mycinamicin hydroxylation and epoxidation reactions

Journal of Biological Chemistry

Volumn 287, Issue 45, 2012, Pages 37880-37890

  Li, Shengying ^a,b   Tietz, Drew R ^c   Rutaganira, Florentine U ^d   Kells, Petrea M ^d   Anzai, Yojiro ^f   Kato, Fumio ^f   Pochapsky, Thomas C ^c   Sherman, David H ^a   Podust, Larissa M ^d,e  

^a UNIVERSITY OF MICHIGAN   (United States)

^b QINGDAO INSTITUTE OF BIOENERGY AND BIOPROCESS TECHNOLOGY   (China)

^c BRANDEIS UNIVERSITY   (United States)

^d University of California at San Francisco   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f TOHO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; EPOXIDATION REACTIONS; MACROLIDES; METHOXY GROUP; PROTEIN ENGINEERING; SUBSTRATE RECOGNITION;

EPOXIDATION; GENETIC ENGINEERING; KETONES;

SUBSTRATES;

CYTOCHROME P450; CYTOCHROME P450 MYCG; HYDROGEN; MACROLIDE; MYCINAMICIN; MYCINAMICIN III; MYCINAMICIN IV; MYCINAMICIN V; UNCLASSIFIED DRUG;

ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME LOCALIZATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE COMPLEX; EPOXIDATION; HYDROXYLATION; IN VITRO STUDY; METABOLITE; MOLECULAR INTERACTION; MOLECULAR MODEL; MOLECULAR RECOGNITION; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; STRUCTURE ANALYSIS;

BACTERIAL PROTEINS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; EPOXY COMPOUNDS; GLYCOSYLATION; HYDROXYLATION; MACROLIDES; MAGNETIC RESONANCE SPECTROSCOPY; METHYLATION; MICROMONOSPORA; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTATION; OXIDATION-REDUCTION; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; SUBSTRATE SPECIFICITY;

EID: 84868333860     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.410340     Document Type: Article

References (60)

1. Satoi, S., Muto, N., Hayashi, M., Fujii, T., and Otani, M. (1980) Mycinamicins, new macrolide antibiotics. I. Taxonomy, production, isolation, characterization, and properties. J. Antibiot. 33, 364-3766
2. Takenaka, S., Yoshida, K., Yamaguchi, O., Shimizu, K., Morohoshi, T., and Kinoshita, K. (1998) Enhancement of mycinamicin production by dotriacolide in Micromonospora griseorubida. FEMS Microbiol. Lett. 167, 95-1000
3. Kinoshita, K., Satoi, S., Hayashi, M., Harada, K., Suzuki, M., and Nakatsu, K. (1985) Mycinamicins, new macrolide antibiotics. VIII. Chemical degradation and absolute configuration of mycinamicins. J. Antibiot. 38, 522-5266
4. Kinoshita, K., Imura, Y., Takenaka, S., and Hayashi, M. (1989)Mycinamicins, new macrolide antibiotics. XI. Isolation and structure elucidation of a key intermediate in the biosynthesis of the mycinamicins, mycinamicin VIII. J. Antibiot. 42, 1869-18722
5. Kinoshita, K., Satoi, S., Hayashi, M., and Nakatsu, K. (1989)Mycinamicins, new macrolide antibiotics. X. X-ray crystallography and the absolute configuration of mycinamicin IV. J. Antibiot. 42, 1003-10055
6. Suzuki, H., Takenaka, S., Kinoshita, K., and Morohoshi, T. (1990) Biosynthesis of mycinamicins by a blocked mutant of Micromonospora griseorubida. J. Antibiot. 43, 1508-15111
7. Kinoshita, K., Takenaka, S., Suzuki, H., Morohoshi, T., and Hayashi, M. (1992) Mycinamicins, new macrolide antibiotics. XIII. Isolation and structures of novel fermentation products from Micromonospora griseorubida (FERM BP-705). J. Antibiot. 45, 1-99
8. Inouye, M., Takada, Y., Muto, N., Beppu, T., and Horinouchi, S. (1994) Characterization and expression of a P-450-like mycinamicin biosynthesis gene using a novel Micromonospora-Escherichia coli shuttle cosmid vector. Mol. Gen. Genet. 245, 456-4644
9. Anzai, Y., Saito, N., Tanaka, M., Kinoshita, K., Koyama, Y., and Kato, F. (2003) Organization of the biosynthetic gene cluster for the polyketide macrolide mycinamicin in Micromonospora griseorubida. FEMS Microbiol. Lett. 218, 135-1411
10. Anzai, Y., Li, S., Chaulagain, M. R., Kinoshita, K., Kato, F., Montgomery, J., and Sherman, D. H. (2008)Functional analysis of MycCI and MycG, cytochrome P450 enzymes involved in biosynthesis of mycinamicin macrolide antibiotics. Chem. Biol. 15, 950-9599
11. Kudo, F., Motegi, A., Mizoue, K., and Eguchi, T. (2010) Cloning and characterization of the biosynthetic gene cluster of 16-membered macrolide antibiotic FD-891. Involvement of a dual functional cytochrome P450 monooxygenase catalyzing epoxidation and hydroxylation. ChemBioChem 11, 1574-15822
12. Carlson, J. C., Li, S., Burr, D. A., and Sherman, D. H. (2009)Isolation and characterization of tirandamycins from a marine-derived Streptomyces sp. J. Nat. Prod. 72, 2076-20799
13. Carlson, J. C., Fortman, J. L., Anzai, Y., Li, S., Burr, D. A., and Sherman, D. H. (2010) Identification of the tirandamycin biosynthetic gene cluster from Streptomyces sp. 307-9. ChemBioChem. 11, 564-5722
14. Carlson, J. C., Li, S., Gunatilleke, S. S., Anzai, Y., Burr, D. A., Podust, L. M., and Sherman, D. H. (2011) Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes. Nat. Chem. 3, 628-6333
15. Zocher, G., Richter, M. E., Mueller, U., and Hertweck, C. (2011) Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 133, 2292-23022
16. He, J., and Hertweck, C. (2003) Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster. Chem. Biol. 10, 1225-12322
17. Müller, M., He, J., and Hertweck, C. (2006) Dissection of the late steps in aureothin biosynthesis. ChemBioChem 7, 37-399
18. Podust, L. M., and Sherman, D. H. (2012) Diversity of P450 enzymes in the biosynthesis of natural products. Nat. Prod. Rep. 29, 1251-12666
19. Crešnar, B., and Petrič, S. (2011) Cytochrome P450 enzymes in the fungal kingdom. Biochim. Biophys. Acta 1814, 29-355
20. Tokai, T., Koshino, H., Takahashi-Ando, N., Sato, M., Fujimura, M., and Kimura, M. (2007) Fusarium Tri4 encodes a key multifunctional cytochrome P450 monooxygenase for four consecutive oxygenation steps in trichothecene biosynthesis. Biochem. Biophys. Res. Commun. 353, 412-4177
21. Seo, J. A., Proctor, R. H., and Plattner, R. D. (2001) Characterization of four clustered and coregulated genes associated with fumonisin biosynthesis in Fusarium verticillioides. Fungal Genet. Biol. 34, 155-1655
22. Bojja, R. S., Cerny, R. L., Proctor, R. H., and Du, L. (2004) Determining the biosynthetic sequence in the early steps of the fumonisin pathway by use of three gene-disruption mutants of Fusarium verticillioides. J. Agric. Food Chem. 52, 2855-28600
23. Proctor, R. H., Plattner, R. D., Desjardins, A. E., Busman, M., and Butchko, R. A. (2006) Fumonisin production in the maize pathogen Fusarium verticillioides. Genetic basis of naturally occurring chemical variation. J. Agric. Food Chem. 54, 2424-24300
24. Tudzynski, B., Rojas, M. C., Gaskin, P., and Hedden, P. (2002) The gibberellin 20-oxidase of Gibberella fujikuroi is a multifunctional monooxygenase. J. Biol. Chem. 277, 21246-212533
25. Tudzynski, B., Hedden, P., Carrera, E., and Gaskin, P. (2001) The P450-4 gene of Gibberella fujikuroi encodes ent-kaurene oxidase in the gibberellin biosynthesis pathway. Appl. Environ. Microbiol. 67, 3514-35222
26. Rojas, M. C., Hedden, P., Gaskin, P., and Tudzynski, B. (2001) The P450-1 gene of Gibberella fujikuroi encodes a multifunctional enzyme in gibberellin biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 98, 5838-58433
27. Tsukada, S., Anzai, Y., Li, S., Kinoshita, K., Sherman, D. H., and Kato, F. (2010) Gene targeting for O-methyltransferase genes, mycE and mycF, on the chromosome of Micromonospora griseorubida producing mycinamicin with a disruption cassette containing the bacteriophage phi C31 attB attachment site. FEMS Microbiol. Lett. 304, 148-1566
28. Anzai, Y., Tsukada, S., Sakai, A., Masuda, R., Harada, C., Domeki, A., Li, S., Kinoshita, K., Sherman, D. H., and Kato, F. (2012) Function of cytochrome P450 enzymes MycCI and MycG in Micromonospora griseorubida, a producer of the macrolide antibiotic mycinamicin. Antimicrob. Agents Chemother. 56, 3648-36566
29. von Kries, J. P., Warrier, T., and Podust, L. M. (2010) Identification of small molecule scaffolds for P450 inhibitors. Curr. Protoc. Microbiol. 16, 17.4.1-17.4.255
30. Omura, T., and Sato, R. (1964) The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J. Biol. Chem. 239, 2379-23855
31. Leslie, A. G. (1992) Recent changes to the MOSFLM package for processing film and image plate data. Joint CCP4 ESF-EAMCB Newslett. Protein Crystallogr. No. 266
32. Holton, J., and Alber, T. (2004) Automated protein crystal structure determination using ELVES. Proc. Natl. Acad. Sci. U.S.A. 101, 1537-15422
33. Yasutake, Y., Imoto, N., Fujii, Y., Fujii, T., Arisawa, A., and Tamura, T. (2007) Crystal structure of cytochrome P450 MoxA from Nonomuraea recticatena (CYP105). Biochem. Biophys. Res. Commun. 361, 876-8822
34. Cowtan, K. (2006) The Buccaneer software for automated model building. Tracing protein chains. Acta Crystallogr. D Biol. Crystallogr. 62, 1002-10111
35. Collaborative Computational Project No. 4 (1994) The CCP4 suite. Programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-7633
36. Emsley, P., and Cowtan, K. (2004) Coot. Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-21322
37. Murshudov, G. N., Vagin, A. A., and Dodson, E. J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-2555
38. Modi, S., Primrose, W. U., Boyle, J. M., Gibson, C. F., Lian, L. Y., and Roberts, G. C. (1995) NMR studies of substrate binding to cytochrome P450 BM3. Comparisons to cytochrome P450cam. Biochemistry 34, 8982-89888
39. Bloembergen, N. (1957) Proton relaxation times in paramagnetic solutions. J. Chem. Phys. 27, 572-5733
40. Solomon, I. (1955) Relaxation processes in a system of 2 spins. Phys. Rev. 99, 559-5655
41. Philson, S. B., Debrunner, P. G., Schmidt, P. G., and Gunsalus, I. C. (1979) The effect of cytochrome P-450cam on the NMR relaxation rate of water protons. J. Biol. Chem. 254, 10173-101799
42. Case, D. A., Darden, T. A., Cheatham, T. E., III, Simmerling, C. L., Wang, J., Duke, R. E., Luo, R., Walker, R. C., Zhang, W., Merz, K. M., Roberts, B. P., Wang, B., Hayik, S., Roitberg, A., Seabra, G., Kolossváry, I., Wong, K. F., Paesani, F., Vanicek, J., Liu, J., Wu, X., Brozell, S. R., Steinbrecher, T., Gohlke, H., Cai, Q., Ye, X., Wang, J., Hsieh, M. J., Cui, G., Roe, D. R., Mathews, D. H., Seetin, M. G., Sagui, C., Babin, V., Luchko, T., Gusarov, S., Kovalenko, A., and Kollman, P. A. (2010) AMBER 11. University of California, San Franciscoo
43. Cupp-Vickery, J. R., and Poulos, T. L. (1995) Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat. Struct. Biol. 2, 144-1533
44. Cupp-Vickery, J. R., Han, O., Hutchinson, C. R., and Poulos, T. L. (1996)Substrate-assisted catalysis in cytochrome P450 eryF. Nat. Struct. Biol. 3, 632-6377
45. Savino, C., Montemiglio, L. C., Sciara, G., Miele, A. E., Kendrew, S. G., Jemth, P., Gianni, S., and Vallone, B. (2009)Investigating the structural plasticity of a cytochrome P450. Three-dimensional structures of P450 EryK and binding to its physiological substrate. J. Biol. Chem. 284, 29170-291799
46. Sherman, D. H., Li, S., Yermalitskaya, L. V., Kim, Y., Smith, J. A., Waterman, M. R., and Podust, L. M. (2006) The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae. J. Biol. Chem. 281, 26289-262977
47. Li, S., Ouellet, H., Sherman, D. H., and Podust, L. M. (2009)Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. J. Biol. Chem. 284, 5723-57300
48. Li, S., Chaulagain, M. R., Knauff, A. R., Podust, L. M., Montgomery, J., and Sherman, D. H. (2009)Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 mono-oxygenase. Proc. Natl. Acad. Sci. U.S.A. 106, 18463-184688
49. Kells, P. M., Ouellet, H., Santos-Aberturas, J., Aparicio, J. F., and Podust, L. M. (2010) Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide pimaricin occurs via a hydroperoxoferric intermediate. Chem. Biol. 17, 841-8511
50. Xu, L. H., Fushinobu, S., Ikeda, H., Wakagi, T., and Shoun, H. (2009)Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis. Conformational flexibility and histidine ligation state. J. Bacteriol. 191, 1211-12199
51. Xu, L. H., Fushinobu, S., Takamatsu, S., Wakagi, T., Ikeda, H., and Shoun, H. (2010) Regio-and stereospecificity of filipin hydroxylation sites revealed by crystal structures of cytochrome P450 105P1 and 105D6 from Streptomyces avermitilis. J. Biol. Chem. 285, 16844-168533
52. Nagano, S., Li, H., Shimizu, H., Nishida, C., Ogura, H., Ortiz de Montellano, P. R., and Poulos, T. L. (2003) Crystal structures of epothilone D-bound, epothilone B-bound, and substrate-free forms of cytochrome P450epoK. J. Biol. Chem. 278, 44886-448933
53. Isin, E. M., and Guengerich, F. P. (2008)Substrate binding to cytochromes P450. Anal. Bioanal. Chem. 392, 1019-10300
54. Johnston, J. B., Ouellet, H., Podust, L. M., and Ortiz de Montellano, P. R. (2011) Structural control of cytochrome P450-catalyzed-hydroxylation. Arch. Biochem. Biophys. 507, 86-944
55. Chen, M. S., and White, M. C. (2010) Combined effects on selectivity in Fe-catalyzed methylene oxidation. Science 327, 566-5711
56. Asciutto, E. K., Young, M. J., Madura, J., Pochapsky, S. S., and Pochapsky, T. C. (2012) Solution structural ensembles of substrate-free cytochrome P450(cam). Biochemistry 51, 3383-33933
57. Wei, J. Y., Pochapsky, T. C., and Pochapsky, S. S. (2005) Detection of a high barrier conformational change in the active site of cytochrome P450cam upon binding of putidaredoxin. J. Am. Chem. Soc. 127, 6974-69766
58. Li, S., Podust, L. M., and Sherman, D. H. (2007) In vitro characterization of a self-sufficient biosynthetic cytochrome P450 PikC fused to a heterologous reductase domain RhFRED. J. Am. Chem. Soc. 129, 12940-129411
59. DeLano, W. L. (2002) The PyMOL Molecular Graphics System, DeLano Scientific LLC, San Carlos, CAA
60. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-16122