Characterization of the P450 monooxygenase NysL, responsible for C-10 hydroxylation during biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei

Applied and Environmental Microbiology

Volumn 72, Issue 4, 2006, Pages 2514-2519

  Volokhan, Olga ^a   Sletta, Håvard ^b   Ellingsen, Trond E ^b   Zotchev, Sergey B ^a  

^a NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^b SINTEF MATERIALS AND CHEMISTRY   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

BIOASSAY; ENZYMES; ESCHERICHIA COLI; HYDROXYLATION; MICROBIOLOGY;

ENZYME ASSAY; GENE REPLACEMENT; NYSL GENE; NYSTATIN PRECURSOR;

GENES;

10 DEOXYNYSTATIN; HISTIDINE; LACTONE; MACROLIDE; NYSTATIN; NYSTATIN DERIVATIVE; P450 MONOOXYGENASE NYSL; POLYKETIDE SYNTHASE; RECOMBINANT ENZYME; UNCLASSIFIED DRUG; UNSPECIFIC MONOOXYGENASE;

ANTIBIOTICS; BACTERIUM; ENZYME; GENE; GENETICS; MICROBIAL ACTIVITY;

ANTIFUNGAL ACTIVITY; ARTICLE; BACTERIAL GENE; BACTERIUM MUTANT; DRUG PURIFICATION; DRUG SYNTHESIS; ENZYME ASSAY; ENZYME MODIFICATION; ENZYME SPECIFICITY; ESCHERICHIA COLI; GENE CLUSTER; GENE IDENTIFICATION; GENE INACTIVATION; HYDROXYLATION; NONHUMAN; NYSL GENE; PROTEIN EXPRESSION; STREPTOMYCES; STREPTOMYCES NOURSEI;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; CYTOCHROME P-450 ENZYME SYSTEM; ESCHERICHIA COLI; GENE DELETION; HYDROXYLATION; KINETICS; NYSTATIN; POLYENES; STREPTOMYCES; SUBSTRATE SPECIFICITY;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; STREPTOMYCES; STREPTOMYCES NOURSEI;

EID: 33646094958     PISSN: 00992240     EISSN: None     Source Type: Journal    
DOI: 10.1128/AEM.72.4.2514-2519.2006     Document Type: Article

References (29)

1. Aparicio, J. F., P. Caffrey, J. A. Gil, and S. B. Zotchev. 2003. Polyene antibiotic biosynthesis gene clusters. Appl. Microbiol. Biotechnol. 61:179-188.
2. Baginski, M., H. Resat, and E. Borowski. 2002. Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels. Biochim. Biophys. Acta 1567:63-78.
3. Bell, S. G., C. F. Harford-Cross, and L. L. Wong. 2001. Engineering the CYP101 system for in vivo oxidation of unnatural substrates. Protein Eng. 14:797-802.
4. Bell, S. G., X. Chen, F. Xu, Z. Rao, and L. L. Wong. 2003. Engineering substrate recognition in catalysis by cytochrome P450cam. Biochem. Soc. Trans. 31:558-562.
5. Betlach, M. C., J. T. Kealey, G. W. Ashley, and R. McDaniel. 1998. Characterization of the macrolide P-450 hydroxylase from Streptomyces venezuelae which converts narbomycin to picromycin. Biochemistry 37:14937-14942.
6. Bischoff, D., S. Pelzer, A. Holtzel, G. J. Nicholson, S. Stockert, W. Wohlleben, G. Jung, and R. D. Sussmuth. 2001. The biosynthesis of vancomycin-type glycopeptide antibiotics-new insights into the cyclization steps. Angew Chem. Int. Ed. Engl. 40:1693-1696.
7. Brautaset, T., O. N. Sekurova, H. Sletta, T. E. Ellingsen, A. R. Strøm, S. Valla, and S. B. Zotchev. 2000. Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chem. Biol. 7:395-403.
8. Brautaset, T., S. E. Borges, H. Sletta, T. E. Ellingsen, and S. B. Zotchev. 2003. Site-specific mutagenesis and domain substitutions in the loading module of the nystatin polyketide synthase, and their effects on nystatin biosynthesis in Streptomyces noursei. J. Biol. Chem. 278:14913-14919.
9. Bruheim, P., S. E. Borgos, P. Tsan, H. Sletta, T. E. Ellingsen, J.-M. Lancelin, and S. B. Zotchev. 2004. Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC 11455 and recombinant strain ERD44 with genetically altered polyketide synthase NysC. Antimicrob. Agents Chemother. 48:4120-4129.
10. Byrne, B., M. Carmody, E. Gibson, B. Rawlings, and P. Caffrey. 2003. Biosynthesis of deoxyamphotericins and deoxyamphoteronolides by engineered strains of Streptomyces nodosus. Chem. Biol. 10:1215-1224.
11. Carmody, M., B. Murphy, B. Byrne, P. Power, D. Rai, B. Rawlings, and P. Caffrey. 2005. Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl groups. J. Biol. Chem. 280:34420-34426.
12. Chen, H., and C. T. Walsh. 2001. Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the aminoacyl enzyme tyrosyl-5-NovH by a cytochrome P450 NovI. Chem. Biol. 8:301-312.
13. Cupp-Vickery, J. R., C. Garcia, A. Hofacre, and K. McGee-Estrada. 2001. Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF. J. Mol. Biol. 311:101-110.
14. Fjaervik, E., and S. B. Zotchev. 2005. Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei. Appl. Microbiol. Biotechnol. 67:436-443.
15. Gaisser, S., R. Lill, J. Staunton, C. Mendez, J. Salas, and P. F. Leadlay. 2002. Parallel pathways for oxidation of 14-membered polyketide macrolactones in Saccharopolyspora erythraea. Mol. Microbiol. 44:771-781.
16. Mansuy, D. 1998. The great diversity of reactions catalyzed by cytochromes P450. Comp. Biochem. Physiol. C 121:5-14.
17. Mendes, M. V., E. Recio, R. Fouces, R. Luiten, J. F. Martin, and J. F. Aparicio. 2001. Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis. Chem. Biol. 8:635-644.
18. Mendes, M. V., N. Anton, J. F. Martin, and J. F. Aparicio. 2005. Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin. Biochem. J. 386:57-62.
19. O'Keefe, D. P., and P. A. Harder. 1991. Occurrence and biological function of cytochrome P450 monooxygenases in the actinomycetes. Mol. Microbiol. 5:2099-2105.
20. Ortiz de Orue Lucana, D., and H. Schrempf. 2000. The DNA-binding characteristics of the Streptomyces reticuli regulator FurS depend on the redox state of its cysteine residues. Mol. Gen. Genet. 264:341-353.
21. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
22. Seco, E. M., S. Fotso, H. Laatsch, and F. Malpartida. 2005. A tailoring activity is responsible for generating polyene amide derivatives in Streptomyces diastaticus var. 108. Chem. Biol. 12:1093-1101.
23. Sekurova, O., H. Sletta, T. E. Ellingsen, S. Valla, and S. Zotchev. 1999. Molecular cloning and analysis of a pleiotropic regulatory gene locus from the nystatin producer Streptomyces noursei ATCC 11455. FEMS Microbiol. Lett. 177:297-304.
24. Sekurova, O. N., T. Brautaset, H. Sletta, S. E. Borgos, O. M. Jakobsen, T. E. Ellingsen, A. R. Strom, S. Valla, and S. B. Zotchev. 2004. In vivo analysis of the regulatory genes in the nystatin biosynthetic gene cluster of Streptomyces noursei ATCC 11455 reveals their differential control over antibiotic biosynthesis. J. Bacteriol. 186:1345-1354.
25. Sletta, H., S. E. Borgos, P. Bruheim, O. N. Sekurova, H. Grasdalen, R. Aune, T. E. Ellingsen, and S. B. Zotchev. 2005. Nystatin biosynthesis and transport: nysH and nysG genes encoding a putative ABC transporter system in Streptomyces noursei ATCC 11455 are required for efficient conversion of 10-deoxynystatin to nystatin. Antimicrob. Agents Chemother. 49:4576-4583.
26. Vosburg, D. A., and C. T. Walsh. 2005. Natural product biosynthetic assembly lines: prospects and challenges for reprogramming. Ernst Schering Res. Found. Workshop 51:261-284.
27. Walczak, R. J., M. L. Dickens, N. D. Priestley, and W. R. Strohl. 1999. Purification, properties, and characterization of recombinant Streptomyces sp. strain CS DoxA, a cytochrome P-450 catalyzing multiple steps in doxorubicin biosynthesis. J. Bacteriol. 181:298-304.
28. Xue, Y., D. Wilson, L. Zhao, H. Liu, and D. H. Sherman. 1998. Hydroxylation of macrolactones YC-17 and narbomycin is mediated by the pikC-encoded cytochrome P450 in Streptomyces venezuelae. Chem. Biol. 5:661-667.
29. Zotchev, S., K. Haugan, O. Sekurova, H. Sletta, T. E. Ellingsen, and S. Valla. 2000. Identification of a gene cluster for antibacterial polyketide-derived antibiotic biosynthesis in the nystatin producer Streptomyces noursei ATCC 11455. Microbiology 146:611-619.