Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: Analysis of the enzymatic domains in the modular polyketide synthase

Gene

Volumn 169, Issue 1, 1996, Pages 9-16

  Aparicio, Jesús F ^a   Molnár, István ^a   Schwecke, Torsten ^a   König, Ariane ^a   Haydock, Stephen F ^a   Khaw, Lake Ee ^a   Staunton, James ^a   Leadlay, Peter F ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Fatty acid; FK506; Immunosuppressant macrolide; Sequence alignment

Indexed keywords

IMMUNOSUPPRESSIVE AGENT; MACROLIDE; POLYKETIDE SYNTHASE; RAPAMYCIN; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; GENE CLUSTER; GENETIC ORGANIZATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; SEQUENCE HOMOLOGY; STREPTOMYCES HYGROSCOPICUS;

EID: 0029872079     PISSN: 03781119     EISSN: None     Source Type: Journal    
DOI: 10.1016/0378-1119(95)00800-4     Document Type: Article

References (25)

1. Aparicio, J.F., Caffrey, P., Marsden, A.F.A., Staunton. J. and Leadlay, P.F.: Limited proteolysis and active-site studies of the first multienzyme component of the erythromycin-producing polyketide synthase. J. Biol. Chem. 269 (1994) 8524-8528.
2. Bevitt, D.J., Cortés, J., Haydock, S.F. and Leadlay, P.F.: 6-Deoxyerythronolide B synthase 2 from Saccharopolyspora erythraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme. Eur. J. Biochem. 204 (1992) 39-49.
3. Caffrey, P., Bevitt, D.J., Staunton, J. and Leadlay, P.F.: Identification of DEBS1, DEBS2 and DEBS3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. FEBS Lett. 304 (1992) 225-228.
4. Cortés, J., Haydock, S.F., Roberts, G.A., Bevitt, D.J. and Leadlay, P.F.: An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348 (1990) 176-178.
5. Criado, L.M., Martin, J.F. and Gil, J.A.: The pab gene of Streptomyces griseus, encoding p-aminobenzoic acid synthase, is located between genes possibly involved in candicidin biosynthesis. Gene 126 (1993) 135-139.
6. Donadio, S. and Katz, L.: Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea. Gene 111 (1992) 51-60.
7. Donadio, S., Staver, M.J., McAlpine, J.B., Swanson, S.J. and Katz, L.: Modular organization of the genes required for complex polyketide biosynthesis. Science 252 (1991) 675-679.
8. Haydock, S., Aparicio, J.F., Molnár, I., Schwecke, T., König, A., Marsden, A.F.A., Galloway, I.S., Staunton, J. and Leadlay, P.F.: Divergent structural motifs correlated with the substrate specificity of (methyl)malonyl-CoA: acyl carrier protein transacylase domains in modular polyketide synthases. FEBS Lett. 374 (1995) 246-248.
9. Hu, Z., Bao, K., Zhou, X., Zhou, Q., Hopwood, D.A., Kieser, T. and Deng, Z.: Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR-008. Mol. Microbiol. (1994) 163-172.
10. MacNeil, D.J., Occi, J.L., Gewain, K.M., MacNeil, T., Gibbons, P.H., Ruby, C.L. and Danis, S.J.: Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. Gene 115 (1992) 119-125.
11. MacNeil, D.J., Occi, J.L., Gewain, K.M. and MacNeil, T.: Correlation of the avermectin polyketide synthase genes to the avermectin structure-implications for designing novel avermectins. Ann. N.Y. Acad. Sci. 721 (1994) 123-132.
12. Marsden, A.F.A, Caffrey, P., Aparicio, J.F., Loughran, M.S., Staunton, J. and Leadlay, P.F.: Stereospecific acyl transfers on the erythromycin-producing polyketide synthase. Science 263 (1994) 378-380.
13. Molnár, I., Aparicio, J.F., Haydock, S.F., Khaw, L.E., Schwecke, T., König, A., Staunton, J. and Leadlay, P.F.: Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase. Gene 169 (1996) 1-7.
14. Moore, B.S., Cho, H., Casati, R., Kennedy, E., Reynolds, K.A., Mocek, U., Beale, J.M. and Floss, H.G.: Biosynthetic studies on ansatrienin A. Formation of the cyclohexanecarboxylic acid moiety. J. Am. Chem. Soc. 115 (1993) 5254-5266.
15. Paiva, N.L., Demain, A.L. and Roberts, M.F.: The immediate precursor of the nitrogen-containing ring of rapamycin is free pipecolic acid. Enzyme Microb. Technol. 15 (1993a) 581-585.
16. Paiva, N.L., Roberts, M.F. and Demain, A.L.: The cyclohexane moiety of rapamycin is derived from shikimic acid in Streptomyces hygroscopicus. J. Ind. Microbiol. 12 (1993b) 423-428.
17. Reynolds, K.A., Wang, P., Fox, K.M., Speedie, M.K., Lam, Y. and Floss, H.G.: Purification and characterization of a novel enoyl coenzyme A reductase from Streptomyces collinus. J. Bacteriol. 174 (1992) 3850-3854.
18. Schwecke, T., Aparicio, J.F., Molnár, I., König, A., Khaw, L.E., Haydock, S.F., Oliynyk, M., Caffrey, P., Cortés, J., Lester, J.B., Böhm, G.A., Staunton, J. and Leadlay, P.F.: The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc. Natl. Acad. Sci. USA 92 (1995) 7839-7843.
19. Scrutton, N.S., Berry, A. and Perham, R.N.: Redesign of the coenzyme specificity of a dehydrogenase by protein engineering. Nature 343 (1990) 38-43.
20. Serre, L., Verbree, E.C., Dauter, Z., Stuitje, A.R. and Derewenda, Z.S.: The Escherichia coli malonyl-CoA:acyl carrier protein transacylase at 1.5 Å resolution. J. Biol. Chem. 270 (1995) 12961-12964.
21. Swan, D.G., Rodríguez, A.M., Vilches, C., Méndez, C. and Salas, J.A.: Characterisation of a Streptomyces antibioticus gene encoding a type I polyketide synthase which has an unusual coding sequence. Mol. Gen. Genet. 242 (1994) 358-362.
22. Tai, M.H., Chirala, S.S. and Wakil, S.J.: Roles of Ser (101), Asp (236), and His (237) in catalysis of thioesterase-II and of the C-terminal region of the enzyme in its interaction with fatty-acid synthase. Proc. Natl. Acad. Sci. USA 90 (1993) 1852-1856.
23. Wallace, K.K., Reynolds, K.A., Koch, K., McArthur, H.A.I., Brown, M.S., Wax, R.G. and Moore, B.S.: Biosynthetic-studies of ascomycin (FK520) - formation of the (1R,3R,4R)-3,4-dihydroxycyclohexanecarboxylic acid-derived moiety. J. Am. Chem. Soc. 116 (1994) 11600-11601.
24. Wakil, S.J.: Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28 (1989) 4523-4530.
25. Witkowski, A., Witkowska, H.E. and Smith, S.: Re-engineering the specificity of a serine active-site enzyme, 2: Active-site mutations convert a hydrolase to a transferase. J. Biol. Chem. 269 (1994) 379-383.