A close look at a ketosynthase from a trans-acyltransferase modular polyketide synthase

Structure

Volumn 22, Issue 3, 2014, Pages 444-451

  Gay, Darren C ^a   Gay, Glen ^a   Axelrod, Abram J ^b   Jenner, Matthew ^c   Kohlhaas, Christoph ^d   Kampa, Annette ^d   Oldham, Neil J ^c   Piel, Jörn ^d,e   Keatinge Clay, Adrian T ^a,b  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b University of Texas at Austin   (United States)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^d UNIVERSITY OF BONN   (Germany)

^e ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL ENZYME; CYSTEINE; KETOSYNTHASE; POLYKETIDE; POLYKETIDE SYNTHASE; SERINE; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; CRYSTAL STRUCTURE; ENZYME SPECIFICITY; ENZYME STRUCTURE; MASS SPECTROMETRY; MUTANT; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CHEMICAL STRUCTURE; CHEMISTRY; ENZYME ACTIVE SITE; GENETICS; METABOLISM; MOLECULAR GENETICS; MUTATION; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; CYSTEINE; MASS SPECTROMETRY; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; POLYKETIDE SYNTHASES; PROTEIN CONFORMATION; SERINE; SUBSTRATE SPECIFICITY;

EID: 84896730719     PISSN: 09692126     EISSN: 18784186     Source Type: Journal    
DOI: 10.1016/j.str.2013.12.016     Document Type: Article

References (25)

1. T. Bretschneider, J.B. Heim, D. Heine, R. Winkler, B. Busch, B. Kusebauch, T. Stehle, G. Zocher, and C. Hertweck Vinylogous chain branching catalysed by a dedicated polyketide synthase module Nature 502 2013 124 128
2. R.A. Butcher, F.C. Schroeder, M.A. Fischbach, P.D. Straight, R. Kolter, C.T. Walsh, and J. Clardy The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis Proc. Natl. Acad. Sci. USA 104 2007 1506 1509
3. C.T. Calderone, W.E. Kowtoniuk, N.L. Kelleher, C.T. Walsh, and P.C. Dorrestein Convergence of isoprene and polyketide biosynthetic machinery: isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis Proc. Natl. Acad. Sci. USA 103 2006 8977 8982
4. C.T. Calderone, S.B. Bumpus, N.L. Kelleher, C.T. Walsh, and N.A. Magarvey A ketoreductase domain in the PksJ protein of the bacillaene assembly line carries out both alpha- and beta-ketone reduction during chain growth Proc. Natl. Acad. Sci. USA 105 2008 12809 12814
5. X.H. Chen, J. Vater, J. Piel, P. Franke, R. Scholz, K. Schneider, A. Koumoutsi, G. Hitzeroth, N. Grammel, and A.W. Strittmatter et al. Structural and functional characterization of three polyketide synthase gene clusters in Bacillus amyloliquefaciens FZB 42 J. Bacteriol. 188 2006 4024 4036
6. Y.Q. Cheng, G.L. Tang, and B. Shen Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis Proc. Natl. Acad. Sci. USA 100 2003 3149 3154
7. M. Jenner, S. Frank, A. Kampa, C. Kohlhaas, P. Pöplau, G.S. Briggs, J. Piel, and N.J. Oldham Substrate specificity in ketosynthase domains from trans-AT polyketide synthases Angew. Chem. Int. Ed. Engl. 52 2013 1143 1147
8. A.T. Keatinge-Clay The structures of type I polyketide synthases Nat. Prod. Rep. 29 2012 1050 1073
9. A.T. Keatinge-Clay, A.A. Shelat, D.F. Savage, S.C. Tsai, L.J. Miercke, J.D. O'Connell 3rd, C. Khosla, and R.M. Stroud Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase Structure 11 2003 147 154
10. C. Kohlhaas, M. Jenner, A. Kampa, G.S. Briggs, J.P. Afonso, J. Piel, and N.J. Oldham Substrate specificity of ketosynthase domains in trans-AT polyketide synthases: amino acid-containing acyl chains Chem. Sci. 4 2013 3212 3217
11. T. Maier, M. Leibundgut, and N. Ban The crystal structure of a mammalian fatty acid synthase Science 321 2008 1315 1322
12. J. Moldenhauer, X.H. Chen, R. Borriss, and J. Piel Biosynthesis of the antibiotic bacillaene, the product of a giant polyketide synthase complex of the trans-AT family Angew. Chem. Int. Ed. Engl. 46 2007 8195 8197
13. J. Moldenhauer, D.C. Götz, C.R. Albert, S.K. Bischof, K. Schneider, R.D. Süssmuth, M. Engeser, H. Gross, G. Bringmann, and J. Piel The final steps of bacillaene biosynthesis in Bacillus amyloliquefaciens FZB42: direct evidence for β,γ dehydration by a trans-acyltransferase polyketide synthase Angew. Chem. Int. Ed. Engl. 49 2010 1465 1467
14. E.M. Musiol, T. Härtner, A. Kulik, J. Moldenhauer, J. Piel, W. Wohlleben, and T. Weber Supramolecular templating in kirromycin biosynthesis: the acyltransferase KirCII loads ethylmalonyl-CoA extender onto a specific ACP of the trans-AT PKS Chem. Biol. 18 2011 438 444
15. T. Nguyen, K. Ishida, H. Jenke-Kodama, E. Dittmann, C. Gurgui, T. Hochmuth, S. Taudien, M. Platzer, C. Hertweck, and J. Piel Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection Nat. Biotechnol. 26 2008 225 233
16. J.G. Olsen, A. Kadziola, P. von Wettstein-Knowles, M. Siggaard-Andersen, and S. Larsen Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery Structure 9 2001 233 243
17. G. Pappenberger, J. Benz, B. Gsell, M. Hennig, A. Ruf, M. Stihle, R. Thoma, and M.G. Rudolph Structure of the human fatty acid synthase KS-MAT didomain as a framework for inhibitor design J. Mol. Biol. 397 2010 508 519
18. P.S. Patel, S. Huang, S. Fisher, D. Pirnik, C. Aklonis, L. Dean, E. Meyers, P. Fernandes, and F. Mayerl Bacillaene, a novel inhibitor of procaryotic protein synthesis produced by Bacillus subtilis: production, taxonomy, isolation, physico-chemical characterization and biological activity J. Antibiot. 48 1995 997 1003
19. J. Piel Biosynthesis of polyketides by trans-AT polyketide synthases Nat. Prod. Rep. 27 2010 996 1047
20. J.J. Reddick, S.A. Antolak, and G.M. Raner PksS from Bacillus subtilis is a cytochrome P450 involved in bacillaene metabolism Biochem. Biophys. Res. Commun. 358 2007 363 367
21. Y. Tang, C.-Y. Kim, I.I. Mathews, D.E. Cane, and C. Khosla The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase Proc. Natl. Acad. Sci. USA 103 2006 11124 11129
22. Y. Tang, A.Y. Chen, C.-Y. Kim, D.E. Cane, and C. Khosla Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase Chem. Biol. 14 2007 931 943
23. P. von Wettstein-Knowles, J.G. Olsen, K.A. McGuire, and A. Henriksen Fatty acid synthesis. Role of active site histidines and lysine in Cys-His-His-type beta-ketoacyl-acyl carrier protein synthases FEBS J. 273 2006 695 710
24. F.T. Wong, X. Jin, I.I. Mathews, D.E. Cane, and C. Khosla Structure and mechanism of the trans-acting acyltransferase from the disorazole synthase Biochemistry 50 2011 6539 6548
25. Y.-M. Zhang, J. Hurlbert, S.W. White, and C.O. Rock Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae J. Biol. Chem. 281 2006 17390 17399