Architecture of the polyketide synthase module: Surprises from electron cryo-microscopy

Current Opinion in Structural Biology

Volumn 31, Issue , 2015, Pages 9-19

  Smith, Janet L ^a,b   Skiniotis, Georgios ^a,b   Sherman, David H ^a,b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIMER; FATTY ACID SYNTHASE; MONOMER; POLYKETIDE SYNTHASE; ACYL CARRIER PROTEIN;

ALPHA HELIX; BETA SHEET; BIOSYNTHESIS; CATALYSIS; CONFORMATIONAL TRANSITION; CRYOELECTRON MICROSCOPY; CRYSTAL STRUCTURE; CRYSTALLIZATION; DIMERIZATION; ENZYME STRUCTURE; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; REVIEW; X RAY CRYSTALLOGRAPHY; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; MOLECULAR EVOLUTION; PROCEDURES; PROTEIN TERTIARY STRUCTURE;

METAZOA;

ACYL CARRIER PROTEIN; ANIMALS; CRYOELECTRON MICROSCOPY; EVOLUTION, MOLECULAR; HUMANS; POLYKETIDE SYNTHASES; PROTEIN STRUCTURE, TERTIARY;

EID: 84924902585     PISSN: 0959440X     EISSN: 1879033X     Source Type: Journal    
DOI: 10.1016/j.sbi.2015.02.014     Document Type: Review

References (61)

1. Newman D.J., Cragg G.M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012, 75:311-335.
2. Cragg G.M., Grothaus P.G., Newman D.J. New horizons for old drugs and drug leads. J Nat Prod 2014, 77:703-723.
3. Poust S., Hagen A., Katz L., Keasling J.D. Narrowing the gap between the promise and reality of polyketide synthases as a synthetic biology platform. Curr Opin Biotechnol 2014, 30C:32-39.
4. Cimermancic P., Medema M.H., Claesen J., Kurita K., Wieland Brown L.C., Mavrommatis K., Pati A., Godfrey P.A., Koehrsen M., Clardy J., Birren B.W., et al. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 2014, 158:412-421.
5. Donia M.S., Cimermancic P., Schulze C.J., Wieland Brown L.C., Martin J., Mitreva M., Clardy J., Linington R.G., Fischbach M.A. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 2014, 158:1402-1414.
6. Akey D.L., Gehret J.J., Khare D., Smith J.L. Insights from the sea: structural biology of marine polyketide synthases. Nat Prod Rep 2012, 29:1038-1049.
7. Keatinge-Clay A.T. The structures of type I polyketide synthases. Nat Prod Rep 2012, 29:1050-1073.
8. Dutta S., Whicher J.R., Hansen D.A., Hale W.A., Chemler J.A., Congdon G.R., Narayan A.R., Håkansson K., Sherman D.H., Smith J.L., Skiniotis G. Structure of a modular polyketide synthase. Nature 2014, 510:512-517.
9. Whicher J.R., Dutta S., Hansen D.A., Hale W.A., Chemler J.A., Dosey A.M., Narayan A.R., Håkansson K., Sherman D.H., Smith J.L., Skiniotis G. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature 2014, 510:560-564.
10. Khosla C., Herschlag D., Cane D.E., Walsh C.T. Assembly line polyketide synthases: mechanistic insights and unsolved problems. Biochemistry 2014, 53:2875-2883.
11. Liscombe D.K., Louie G.V., Noel J.P. Architectures, mechanisms and molecular evolution of natural product methyltransferases. Nat Prod Rep 2012, 29:1238-1250.
12. Blasiak L.C., Drennan C.L. Structural perspective on enzymatic halogenation. Acc Chem Res 2009, 42:147-155.
13. Calderone C.T. Isoprenoid-like alkylations in polyketide biosynthesis. Nat Prod Rep 2008, 25:845-853.
14. Nguyen T., Ishida K., Jenke-Kodama H., Dittmann E., Gurgui C., Hochmuth T., Taudien S., Platzer M., Hertweck C., Piel J. Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol 2008, 26:225-233.
15. Singh S., Phillips G.N., Thorson J.S. The structural biology of enzymes involved in natural product glycosylation. Nat Prod Rep 2012, 29:1201-1237.
16. Podust L.M., Sherman D.H. Diversity of P450 enzymes in the biosynthesis of natural products. Nat Prod Rep 2012, 29:1251-1266.
17. Buchholz T.J., Geders T.W., Bartley F.E., Reynolds K.A., Smith J.L., Sherman D.H. Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains. ACS Chem Biol 2009, 4:41-52.
18. Broadhurst R.W., Nietlispach D., Wheatcroft M.P., Leadlay P.F., Weissman K.J. The structure of docking domains in modular polyketide synthases. Chem Biol 2003, 10:723-731.
19. Whicher J.R., Smaga S.S., Hansen D.A., Brown W.C., Gerwick W.H., Sherman D.H., Smith J.L. Cyanobacterial polyketide synthase docking domains: a tool for engineering natural product biosynthesis. Chem Biol 2013, 20:1340-1351.
20. Smith S., Tsai S.C. The type I fatty acid and polyketide synthases: a tale of two megasynthases. Nat Prod Rep 2007, 24:1041-1072.
21. Maier T., Jenni S., Ban N. Architecture of mammalian fatty acid synthase at 4.5Å resolution. Science 2006, 311:1258-1262.
22. Tang Y., Kim C.Y., Mathews I.I., Cane D.E., Khosla C. The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Proc Natl Acad Sci USA 2006, 103:11124-11129.
23. Keatinge-Clay A.T., Stroud R.M. The structure of a ketoreductase determines the organization of the β-carbon processing enzymes of modular polyketide synthases. Structure 2006, 14:737-748.
24. Kao C.M., Pieper R., Cane D.E., Khosla C. Evidence for two catalytically independent clusters of active sites in a functional modular polyketide synthase. Biochemistry 1996, 35:12363-12368.
25. Staunton J., Caffrey P., Aparicio J.F., Roberts G.A., Bethell S.S., Leadlay P.F. Evidence for a double-helical structure for modular polyketide synthases. Nat Struct Biol 1996, 3:188-192.
26. Tang Y., Chen A.Y., Kim C.Y., Cane D.E., Khosla C. Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem Biol 2007, 14:931-943.
27. Maier T., Leibundgut M., Ban N. The crystal structure of a mammalian fatty acid synthase. Science 2008, 321:1315-1322.
28. Zheng J., Gay D.C., Demeler B., White M.A., Keatinge-Clay A.T. Divergence of multimodular polyketide synthases revealed by a didomain structure. Nat Chem Biol 2012, 8:615-621.
29. Akey D.L., Razelun J.R., Tehranisa J., Sherman D.H., Gerwick W.H., Smith J.L. Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway. Structure 2010, 18:94-105.
30. Tsai S.C., Miercke L.J., Krucinski J., Gokhale R., Chen J.C., Foster P.G., Cane D.E., Khosla C., Stroud R.M. Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. Proc Natl Acad Sci USA 2001, 98:14808-14813.
31. Zhang W., Chakravarty B., Zheng F., Gu Z., Wu H., Mao J., Wakil S.J., Quiocho F.A. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-γ-linolenic acid. Proc Natl Acad Sci USA 2011, 108:15757-15762.
32. Davison J., Dorival J., Rabeharindranto H., Mazon H., Chagot B., Gruez A., Weissman K.J. Insights into the function of trans-acyl transferase polyketide synthases from the SAXS structure of a complete module. Chem Sci 2014, 5:3081-3095.
33. Edwards A.L., Matsui T., Weiss T.M., Khosla C. Architectures of whole-module and bimodular proteins from the 6-deoxyerythronolide B synthase. J Mol Biol 2014, 426:2229-2245.
34. Asturias F.J., Chadick J.Z., Cheung I.K., Stark H., Witkowski A., Joshi A.K., Smith S. Structure and molecular organization of mammalian fatty acid synthase. Nat Struct Mol Biol 2005, 12:225-232.
35. Brignole E.J., Smith S., Asturias F.J. Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol 2009, 16:190-197.
36. Xue Y., Wilson D., Sherman D.H. Genetic architecture of the polyketide synthases for methymycin and pikromycin series macrolides. Gene 2000, 245:203-211.
37. Cortes J., Haydock S.F., Roberts G.A., Bevitt D.J., Leadlay P.F. An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 1990, 348:176-178.
38. Aldrich C.C., Beck B.J., Fecik R.A., Sherman D.H. Biochemical investigation of pikromycin biosynthesis employing native penta- and hexaketide chain elongation intermediates. J Am Chem Soc 2005, 127:8441-8452.
39. Aldrich C.C., Venkatraman L., Sherman D.H., Fecik R.A. Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide. J Am Chem Soc 2005, 127:8910-8911.
40. Campbell M.G., Cheng A., Brilot A.F., Moeller A., Lyumkis D., Veesler D., Pan J., Harrison S.C., Potter C.S., Carragher B., Grigorieff N. Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure 2012, 20:1823-1828.
41. Li X., Mooney P., Zheng S., Booth C.R., Braunfeld M.B., Gubbens S., Agard D.A., Cheng Y. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat Methods 2013, 10:584-590.
42. Henderson R. Structural biology: ion channel seen by electron microscopy. Nature 2013, 504:93-94.
43. Kühlbrandt W. Biochemistry. The resolution revolution. Science 2014, 343:1443-1444.
44. Kühlbrandt W. Cryo-EM enters a new era. Elife 2014, 3:e03678.
45. Liao M., Cao E., Julius D., Cheng Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 2013, 504:107-112.
46. Lu P., Bai X.C., Ma D., Xie T., Yan C., Sun L., Yang G., Zhao Y., Zhou R., Scheres S.H., Shi Y. Three-dimensional structure of human γ-secretase. Nature 2014, 512:166-170.
47. Bergeret F., Gavalda S., Chalut C., Malaga W., Quemard A., Pedelacq J.D., Daffe M., Guilhot C., Mourey L., Bon C. Biochemical and structural study of the atypical acyltransferase domain from the mycobacterial polyketide synthase Pks13. J Biol Chem 2012, 287:33675-33690.
48. Park H., Kevany B.M., Dyer D.H., Thomas M.G., Forest K.T. A polyketide synthase acyltransferase domain structure suggests a recognition mechanism for its hydroxymalonyl-acyl carrier protein substrate. PLOS ONE 2014, 9:e110965.
49. Wong F.T., Jin X., Mathews I.I., Cane D.E., Khosla C. Structure and mechanism of the trans-acting acyltransferase from the disorazole synthase. Biochemistry 2011, 50:6539-6548.
50. Bretschneider T., Heim J.B., Heine D., Winkler R., Busch B., Kusebauch B., Stehle T., Zocher G., Hertweck C. Vinylogous chain branching catalysed by a dedicated polyketide synthase module. Nature 2013, 502:124-128.
51. Gay D.C., Gay G., Axelrod A.J., Jenner M., Kohlhaas C., Kampa A., Oldham N.J., Piel J., Keatinge-Clay A.T. A close look at a ketosynthase from a trans-acyltransferase modular polyketide synthase. Structure 2014, 22:444-451.
52. Zheng J., Fage C.D., Demeler B., Hoffman D.W., Keatinge-Clay A.T. The missing linker: a dimerization motif located within polyketide synthase modules. ACS Chem Biol 2013, 8:1263-1270.
53. Hansen D.A., Rath C.M., Eisman E.B., Narayan A.R., Kittendorf J.D., Mortison J.D., Yoon Y.J., Sherman D.H. Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin, and ketomethymycin. J Am Chem Soc 2013, 135:11232-11238.
54. Gokulan K., O'Leary S.E., Russell W.K., Russell D.H., Lalgondar M., Begley T.P., Ioerger T.R., Sacchettini J.C. Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones. J Biol Chem 2013, 288:16484-16494.
55. Dutta D., Bhattacharyya S., Roychowdhury A., Biswas R., Das A.K. Crystal structure of hexanoyl-CoA bound to β-ketoacyl reductase FabG4 of Mycobacterium tuberculosis. Biochem J 2013, 450:127-139.
56. Keatinge-Clay A.T. A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem Biol 2007, 14:898-908.
57. Caffrey P. Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketide synthases. Chembiochem 2003, 4:654-657.
58. Bonnett S.A., Whicher J.R., Papireddy K., Florova G., Smith J.L., Reynolds K.A. Structural and stereochemical analysis of a modular polyketide synthase ketoreductase domain required for the generation of a cis-alkene. Chem Biol 2013, 20:772-783.
59. Chen A.Y., Schnarr N.A., Kim C.Y., Cane D.E., Khosla C. Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase. J Am Chem Soc 2006, 128:3067-3074.
60. Gu L., Wang B., Kulkarni A., Geders T.W., Grindberg R.V., Gerwick L., Hakansson K., Wipf P., Smith J.L., Gerwick W.H., Sherman D.H. Metamorphic enzyme assembly in polyketide diversification. Nature 2009, 459:731-735.
61. Gu L., Wang B., Kulkarni A., Gehret J.J., Lloyd K.R., Gerwick L., Gerwick W.H., Wipf P., Hakansson K., Smith J.L., Sherman D.H. Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis. J Am Chem Soc 2009, 131:16033-16035.