Combinatorial Generation of Chemical Diversity by Redox Enzymes in Chaetoviridin Biosynthesis

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2016 Mar 10

PMID 26959241

Citations 18

Authors

Michio Sato

Jaclyn M Winter

Shinji Kishimoto

Hiroshi Noguchi

Yi Tang

Kenji Watanabe

Affiliations

Soon will be listed here.

Abstract

Chaetoviridins constitute a large family of structurally related secondary metabolites isolated from Chaetomium fungi. To elucidate the biosynthesis pathway and understand how the chemical diversity of chaetoviridins is generated, gene deletion and in vitro characterization of the four post-PKS modifications enzymes were undertaken. CazL and CazP were identified to have substrate promiscuity that facilitates the formation of nonchlorinated analogues. In addition, enzymatic oxidation and reduction combined with spontaneous dehydration and lactonization of the intermediates further expand the chemical diversity.

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References

Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden T . NCBI BLAST: a better web interface. Nucleic Acids Res. 2008; 36(Web Server issue):W5-9. PMC: 2447716. DOI: 10.1093/nar/gkn201. View

Wei W, Yao Z . Synthesis studies toward chloroazaphilone and vinylogous gamma-pyridones: two common natural product core structures. J Org Chem. 2005; 70(12):4585-90. DOI: 10.1021/jo050414g. View

Fischbach M, Clardy J . One pathway, many products. Nat Chem Biol. 2007; 3(7):353-5. DOI: 10.1038/nchembio0707-353. View

Ishiuchi K, Nakazawa T, Yagishita F, Mino T, Noguchi H, Hotta K . Combinatorial generation of complexity by redox enzymes in the chaetoglobosin A biosynthesis. J Am Chem Soc. 2013; 135(19):7371-7. DOI: 10.1021/ja402828w. View

Borges W, Mancilla G, Guimaraes D, Duran-Patron R, Collado I, Pupo M . Azaphilones from the endophyte Chaetomium globosum. J Nat Prod. 2011; 74(5):1182-7. DOI: 10.1021/np200110f. View

Winter J, Sato M, Sugimoto S, Chiou G, Garg N, Tang Y . Identification and characterization of the chaetoviridin and chaetomugilin gene cluster in Chaetomium globosum reveal dual functions of an iterative highly-reducing polyketide synthase. J Am Chem Soc. 2012; 134(43):17900-3. PMC: 3494086. DOI: 10.1021/ja3090498. View

Nakazawa T, Ishiuchi K, Sato M, Tsunematsu Y, Sugimoto S, Gotanda Y . Targeted disruption of transcriptional regulators in Chaetomium globosum activates biosynthetic pathways and reveals transcriptional regulator-like behavior of aureonitol. J Am Chem Soc. 2013; 135(36):13446-55. DOI: 10.1021/ja405128k. View

Yamada T, Yasuhide M, Shigeta H, Numata A, Tanaka R . Absolute stereostructures of chaetomugilins G and H produced by a marine-fish-derived Chaetomium species. J Antibiot (Tokyo). 2009; 62(7):353-7. DOI: 10.1038/ja.2009.39. View

Zabala A, Xu W, Chooi Y, Tang Y . Characterization of a silent azaphilone gene cluster from Aspergillus niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation. Chem Biol. 2012; 19(8):1049-59. PMC: 3428717. DOI: 10.1016/j.chembiol.2012.07.004. View

10.

Gao J, Yang S, Qin J . Azaphilones: chemistry and biology. Chem Rev. 2013; 113(7):4755-811. DOI: 10.1021/cr300402y. View

11.

Yamada T, Jinno M, Kikuchi T, Kajimoto T, Numata A, Tanaka R . Three new azaphilones produced by a marine fish-derived chaetomium globosum. J Antibiot (Tokyo). 2012; 65(8):413-7. DOI: 10.1038/ja.2012.40. View

12.

Winter J, Cascio D, Dietrich D, Sato M, Watanabe K, Sawaya M . Biochemical and Structural Basis for Controlling Chemical Modularity in Fungal Polyketide Biosynthesis. J Am Chem Soc. 2015; 137(31):9885-93. PMC: 4922798. DOI: 10.1021/jacs.5b04520. View

13.

Chiang Y, Szewczyk E, Davidson A, Keller N, Oakley B, Wang C . A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans. J Am Chem Soc. 2009; 131(8):2965-70. PMC: 2765542. DOI: 10.1021/ja8088185. View

14.

Wang P, Gao X, Tang Y . Complexity generation during natural product biosynthesis using redox enzymes. Curr Opin Chem Biol. 2012; 16(3-4):362-9. PMC: 3415589. DOI: 10.1016/j.cbpa.2012.04.008. View

15.

Wang S, Xu Y, Maine E, Wijeratne E, Espinosa-Artiles P, Gunatilaka A . Functional characterization of the biosynthesis of radicicol, an Hsp90 inhibitor resorcylic acid lactone from Chaetomium chiversii. Chem Biol. 2008; 15(12):1328-38. DOI: 10.1016/j.chembiol.2008.10.006. View