Novel Ketosynthases Catalyzing the Non-Decarboxylative Claisen Condensation

Lixia       Pan; Dengfeng       Yang

doi:10.2174/1570193X16666191002155136

Abstract

In this review, we present the recent advances in unusual novel ketosynthases catalyzing the non-decarboxylative Claisen condensations, including CsyB, MxnB/CorB, Ppys and StlD. The differences are summarized between these non-decarboxylative ketosynthases and the typical decarboxylative ketosynthases. Furthermore, the detailed enzymatic characteristics, structural basis, and catalytic mechanismof these novel ketosynthasesare described. Finally, the prospect of these kind of ketosynthases is discussed.

Keywords: Catalytic mechanism, claisen condensation, condensation reaction head-to-head condensation, novel ketosynthases, polyketide synthase, decarboxylative enzymes.

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[1] 
Heath, R.J.; Rock, C.O. The Claisen condensation in biology. Nat. Prod. Rep.,  2002, 19(5), 581-596.
[http://dx.doi.org/10.1039/b110221b] [PMID: 12430724] 
[2] 
Hertweck, C. The biosynthetic logic of polyketide diversity. Angew. Chem. Int. Ed. Engl.,  2009, 48(26), 4688-4716.
[http://dx.doi.org/10.1002/anie.200806121] [PMID: 19514004] 
[3] 
Morita, H.; Shimokawa, Y.; Tanio, M.; Kato, R.; Noguchi, H.; Sugio, S.; Kohno, T.; Abe, I. A structure-based mechanism for benzalacetone synthase from Rheum palmatum. Proc. Natl. Acad. Sci. USA,  2010, 107(2), 669-673.
[http://dx.doi.org/10.1073/pnas.0909982107] [PMID: 20080733] 
[4] 
Morita, H.; Wanibuchi, K.; Nii, H.; Kato, R.; Sugio, S.; Abe, I. Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa. Proc. Natl. Acad. Sci. USA,  2010, 107(46), 19778-19783.
[http://dx.doi.org/10.1073/pnas.1011499107] [PMID: 21041675] 
[5] 
Morita, H.; Yamashita, M.; Shi, S.P.; Wakimoto, T.; Kondo, S.; Kato, R.; Sugio, S.; Kohno, T.; Abe, I. Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase. Proc. Natl. Acad. Sci. USA,  2011, 108(33), 13504-13509.
[http://dx.doi.org/10.1073/pnas.1107782108] [PMID: 21825160] 
[6] 
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(7506), 560-564.
[http://dx.doi.org/10.1038/nature13409] [PMID: 24965656] 
[7] 
Modis, Y.; Wierenga, R.K. Crystallographic analysis of the reaction pathway of Zoogloea ramigera biosynthetic thiolase. J. Mol. Biol.,  2000, 297(5), 1171-1182.
[http://dx.doi.org/10.1006/jmbi.2000.3638] [PMID: 10764581] 
[8] 
Mori, T.; Yang, D.; Matsui, T.; Hashimoto, M.; Morita, H.; Fujii, I.; Abe, I.; Abe, I. Structural basis for the formation of acylalkylpyrones from two β-ketoacyl units by the fungal type III polyketide synthase CsyB. J. Biol. Chem.,  2015, 290(8), 5214-5225.
[http://dx.doi.org/10.1074/jbc.M114.626416] [PMID: 25564614] 
[9] 
Sucipto, H.; Sahner, J.H.; Prusov, E.; Wenzel, S.C.; Hartmann, R.W.; Koehnke, J.; Müller, R. In vitro reconstitution of α-pyrone ring formation in myxopyronin biosynthesis. Chem. Sci. (Camb.),  2015, 6(8), 5076-5085.
[http://dx.doi.org/10.1039/C5SC01013F] [PMID: 29308173] 
[10] 
Zocher, G.; Vilstrup, J.; Heine, D.; Hallab, A.; Goralski, E.; Hertweck, C.; Stahl, M.; Schäberle, T.F.; Stehle, T. Structural basis of head to head polyketide fusion by CorB. Chem. Sci. (Camb.),  2015, 6(11), 6525-6536.
[http://dx.doi.org/10.1039/C5SC02488A] [PMID: 28757960] 
[11] 
Kresovic, D.; Schempp, F.; Cheikh-Ali, Z.; Bode, H.B. A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis. Beilstein J. Org. Chem.,  2015, 11, 1412-1417.
[http://dx.doi.org/10.3762/bjoc.11.152] [PMID: 26425196] 
[12] 
Mori, T.; Awakawa, T.; Shimomura, K.; Saito, Y.; Yang, D.; Morita, H.; Abe, I. Structural insight into the enzymatic formation of bacterial stilbene. Cell Chem. Biol.,  2016, 23(12), 1468-1479.
[http://dx.doi.org/10.1016/j.chembiol.2016.10.010] [PMID: 27866911] 
[13] 
Seshime, Y.; Juvvadi, P.R.; Fujii, I.; Kitamoto, K. Discovery of a novel superfamily of type III polyketide synthases in Aspergillus oryzae. Biochem. Biophys. Res. Commun.,  2005, 331(1), 253-260.
[http://dx.doi.org/10.1016/j.bbrc.2005.03.160] [PMID: 15845386] 
[14] 
Seshime, Y.; Juvvadi, P.R.; Kitamoto, K.; Ebizuka, Y.; Fujii, I. Identification of csypyrone B1 as the novel product of Aspergillus oryzae type III polyketide synthase CsyB. Bioorg. Med. Chem.,  2010, 18(12), 4542-4546.
[http://dx.doi.org/10.1016/j.bmc.2010.04.058] [PMID: 20471846] 
[15] 
Hashimoto, M.; Koen, T.; Takahashi, H.; Suda, C.; Kitamoto, K.; Fujii, I. Aspergillus oryzae CsyB catalyzes the condensation of two β-ketoacyl-CoAs to form 3-acetyl-4-hydroxy-6-alkyl-α-pyrone. J. Biol. Chem.,  2014, 289(29), 19976-19984.
[http://dx.doi.org/10.1074/jbc.M114.569095] [PMID: 24895122] 
[16] 
Mukhopadhyay, J.; Das, K.; Ismail, S.; Koppstein, D.; Jang, M.; Hudson, B.; Sarafianos, S.; Tuske, S.; Patel, J.; Jansen, R.; Irschik, H.; Arnold, E.; Ebright, R.H. The RNA polymerase “switch region” is a target for inhibitors. Cell,  2008, 135(2), 295-307.
[http://dx.doi.org/10.1016/j.cell.2008.09.033] [PMID: 18957204] 
[17] 
Erol, O.; Schäberle, T.F.; Schmitz, A.; Rachid, S.; Gurgui, C.; El Omari, M.; Lohr, F.; Kehraus, S.; Piel, J.; Müller, R.; König, G.M. Biosynthesis of the myxobacterial antibiotic corallopyronin A. ChemBioChem,  2010, 11(9), 1253-1265.
[http://dx.doi.org/10.1002/cbic.201000085] [PMID: 20503218] 
[18] 
Sucipto, H.; Wenzel, S.C.; Müller, R. Exploring chemical diversity of α-pyrone antibiotics: Molecular basis of myxopyronin biosynthesis. ChemBioChem,  2013, 14(13), 1581-1589.
[http://dx.doi.org/10.1002/cbic.201300289] [PMID: 23983106] 
[19] 
Brachmann, A.O.; Brameyer, S.; Kresovic, D.; Hitkova, I.; Kopp, Y.; Manske, C.; Schubert, K.; Bode, H.B.; Heermann, R. Pyrones as bacterial signaling molecules. Nat. Chem. Biol.,  2013, 9(9), 573-578.
[http://dx.doi.org/10.1038/nchembio.1295] [PMID: 23851573] 
[20] 
Brachmann, A.O.; Reimer, D.; Lorenzen, W.; Augusto Alonso, E.; Kopp, Y.; Piel, J.; Bode, H.B. Reciprocal cross talk between fatty acid and antibiotic biosynthesis in a nematode symbiont. Angew. Chem. Int. Ed. Engl.,  2012, 51(48), 12086-12089.
[http://dx.doi.org/10.1002/anie.201205384] [PMID: 23097192] 
[21] 
Fushs, S.W.; Bozhuyuk, K.A.; Kresovic, D.; Grundmann, F.; Dill, V.; Brachmann, A.O.; Waterfield, N.; Bode, H.B. Formation of 1,3-cyclohexanediones and resorcinols catalyzed by a widely occuring ketosynthase. Angew. Chem. Int. Ed.,  2013, 52(13), 4108-4112.
[22] 
Yang, D.; Mori, T.; Matsui, T.; Hashimoto, M.; Morita, H.; Fujii, I.; Abe, I. Expression, purification and crystallization of a fungal type III polyketide synthase that produces the csypyrones. Acta Crystallogr. F Struct. Biol. Commun.,  2014, 70(Pt 6), 730-733.
[http://dx.doi.org/10.1107/S2053230X14008516] [PMID: 24915080] 
[23] 
Goblirsch, B.R.; Frias, J.A.; Wackett, L.P.; Wilmot, C.M. Crystal structures of Xanthomonas campestris OleA reveal features that promote head-to-head condensation of two long-chain fatty acids. Biochemistry,  2012, 51(20), 4138-4146.
[http://dx.doi.org/10.1021/bi300386m] [PMID: 22524624] 

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DOI https://dx.doi.org/10.2174/1570193X16666191002155136	Print ISSN 1570-193X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6298

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Novel Ketosynthases Catalyzing the Non-Decarboxylative Claisen Condensation

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