Elucidation of the Concise Biosynthetic Pathway of the Communesin Indole Alkaloids†
Dr. Hsiao-Ching Lin
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorDr. Grace Chiou
Department of Chemistry and Biochemistry, University of California, Los Angeles
Search for more papers by this authorDr. Yit-Heng Chooi
Plant Sciences Division, Research School of Biology, The Australian National University (Australia)
Search for more papers by this authorDr. Travis C. McMahon
Department of Chemistry and Biochemistry, University of California, Los Angeles
Search for more papers by this authorDr. Wei Xu
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorCorresponding Author
Prof. Neil K. Garg
Department of Chemistry and Biochemistry, University of California, Los Angeles
Neil K. Garg, Department of Chemistry and Biochemistry, University of California, Los Angeles
Yi Tang, Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorCorresponding Author
Prof. Yi Tang
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Neil K. Garg, Department of Chemistry and Biochemistry, University of California, Los Angeles
Yi Tang, Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorDr. Hsiao-Ching Lin
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorDr. Grace Chiou
Department of Chemistry and Biochemistry, University of California, Los Angeles
Search for more papers by this authorDr. Yit-Heng Chooi
Plant Sciences Division, Research School of Biology, The Australian National University (Australia)
Search for more papers by this authorDr. Travis C. McMahon
Department of Chemistry and Biochemistry, University of California, Los Angeles
Search for more papers by this authorDr. Wei Xu
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorCorresponding Author
Prof. Neil K. Garg
Department of Chemistry and Biochemistry, University of California, Los Angeles
Neil K. Garg, Department of Chemistry and Biochemistry, University of California, Los Angeles
Yi Tang, Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorCorresponding Author
Prof. Yi Tang
Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Neil K. Garg, Department of Chemistry and Biochemistry, University of California, Los Angeles
Yi Tang, Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 (USA)
Search for more papers by this authorH-C.L. is supported by the National Science Council of Taiwan (102-2917-I-564-008), and G.C. was supported by a NSF Graduate Research Fellowship (DGE-0707424). This research was supported by NIH grants 1DP1GM106413 and 1R56AI101141. We thank Prof. Brian Stoltz for the gift of aurantioclavine. NMR instrumentation is supported by the NSF (CHE-1048804) and the NCRR (S10RR025631).
Abstract
The communesins are a prominent class of indole alkaloids isolated from Penicillium species. Owing to their daunting structural framework and potential as pharmaceuticals, communesins have inspired numerous synthetic studies. However, the genetic and biochemical basis of communesin biosynthesis has remained unexplored. Herein, we report the identification and characterization of the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We confirmed that communesin is biosynthesized by the coupling of tryptamine and aurantioclavine, two building blocks derived from L-tryptophan. The postmodification steps were mapped by targeted-gene-deletion experiments and the structural elucidation of intermediates and new analogues. Our studies set the stage for the biochemical characterization of communesin biosynthesis. This knowledge will aid our understanding of how nature generates remarkable structural complexity from simple precursors.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange_201411297_sm_miscellaneous_information.pdf2.9 MB | miscellaneous_information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1W. Xu, D. J. Gavia, Y. Tang, Nat. Prod. Rep. 2014, 31, 1474–1487.
- 2
- 2aR. Jadulco, R. A. Edrada, R. Ebel, A. Berg, K. Schaumann, V. Wray, K. Steube, P. Proksch, J. Nat. Prod. 2004, 67, 78–81;
- 2bH. Hayashi, H. Matsumoto, K. Akiyama, Biosci. Biotechnol. Biochem. 2004, 68, 753–756;
- 2cB. Andersen, J. Smedsgaard, J. C. Frisvad, J. Agric. Food Chem. 2004, 52, 2421–2428;
- 2dP. W. Dalsgaard, J. W. Blunt, M. H. G. Munro, J. C. Frisvad, C. Christophersen, J. Nat. Prod. 2005, 68, 258–261;
- 2eL. J. Wigley, P. G. Mantle, D. A. Perry, Phytochemistry 2006, 67, 561–569;
- 2fA. Numata, C. Takahashi, Y. Ito, T. Takada, K. Kawai, Y. Usami, E. Matsumura, M. Imachi, T. Ito, T. Hasegawa, Tetrahedron Lett. 1993, 34, 2355–2358.
- 3
- 3aH. Wu, F. Xue, X. Xiao, Y. Qin, J. Am. Chem. Soc. 2010, 132, 14052–14054;
- 3bJ. Yang, H. Wu, L. Shen, Y. Qin, J. Am. Chem. Soc. 2007, 129, 13794–13795;
- 3cZ. Zuo, W. Xie, D. Ma, J. Am. Chem. Soc. 2010, 132, 13226–13228;
- 3dZ. Zuo, D. Ma, Angew. Chem. Int. Ed. 2011, 50, 12008–12011; Angew. Chem. 2011, 123, 12214–12217;
- 3eP. Liu, J. H. Seo, S. M. Weinreb, Angew. Chem. Int. Ed. 2010, 49, 2000–2003; Angew. Chem. 2010, 122, 2044–2047;
- 3fJ. H. Seo, P. Liu, S. M. Weinreb, J. Org. Chem. 2010, 75, 2667–2680;
- 3gJ. Belmar, R. L. Funk, J. Am. Chem. Soc. 2012, 134, 16941–16943;
- 3hS. L. Crawley, R. L. Funk, Org. Lett. 2003, 5, 3169–3171;
- 3iS.-J. Han, F. Vogt, J. A. May, S. Krishnan, M. Gatti, S. C. Virgil, B. M. Stoltz, J. Org. Chem. 2014, 80, 528–547;
- 3jS.-J. Han, F. Vogt, S. Krishnan, J. A. May, M. Gatti, S. C. Virgil, B. M. Stoltz, Org. Lett. 2014, 16, 3316–3319;
- 3kJ. A. May, R. K. Zeidan, B. M. Stoltz, Tetrahedron Lett. 2003, 44, 1203–1205;
- 3lP. Siengalewicz, T. Gaich, J. Mulzer, Angew. Chem. Int. Ed. 2008, 47, 8170–8176; Angew. Chem. 2008, 120, 8290–8296.
- 4L. J. Wigley, D. A. Perry, P. G. Mantle, Mycol. Res. 2008, 112, 131–137.
- 5J. A. May, B. Stoltz, Tetrahedron 2006, 62, 5262–5271.
- 6I. Kerzaon, Y. F. Pouchus, F. Monteau, B. Le Bizec, M.-R. Nourrisson, J.-F. Biard, O. Grovel, Rapid Commun. Mass Spectrom. 2009, 23, 3928–3938.
- 7K. Blin, M. H. Medema, D. Kazempour, M. A. Fischbach, R. Breitling, E. Takano, T. Weber, Nucleic Acids Res. 2013, 41, W 204–W212.
- 8
- 8aN. Lorenz, J. Olšovská, M. Šulc, P. Tudzynski, Appl. Environ. Microbiol. 2010, 76, 1822–1830;
- 8bK. E. Goetz, C. M. Coyle, J. Z. Cheng, S. E. O’Connor, D. G. Panaccione, Curr. Genet. 2011, 57, 201–211.
- 9C. A. F. Nielsen, C. Folly, A. Hatsch, A. Molt, H. Schröder, S. E. O’Connor, M. Naesby, Microb. Cell Fact. 2014, 13, 95.
- 10I. A. Unsöld, S.-M. Li, Microbiology 2005, 151, 1499–1505.
- 11H.-C. Lin, Y.-H. Chooi, S. Dhingra, W. Xu, A. M. Calvo, Y. Tang, J. Am. Chem. Soc. 2013, 135, 4616–4619.
- 12N. Steffan, A. Grundmann, S. Afiyatullov, H. Ruan, S.-M. Li, Org. Biomol. Chem. 2009, 7, 4082–4087.
- 13D. R. Nelson, Hum. Genomics 2009, 4, 59–65.
Citing Literature
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
