Journal of the American Chemical Society
Communication
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whether linear fragment 10 has transient activity before decay
through intramolecular cyclization.
Taken together, we provide a catalog of small molecules
dependent on the clb genomic island, which has been linked to
long-term persistence of E. coli in the bowel, probiotic activity,
and carcinogenesis. From this clb catalog, we characterized one
known and two previously unknown metabolites and propose
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mutualistic or pathogenic host-bacteria interactions. Our data
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ASSOCIATED CONTENT
* Supporting Information
Experimental and synthetic procedures, NMR and HRMS
characterization of new compounds, supplementary figures and
tables. This material is available free of charge via the Internet
■
S
AUTHOR INFORMATION
Corresponding Author
(20) Brotherton, C. A.; Balskus, E. P. J. Am. Chem. Soc. 2013, 135,
3359.
■
(21) Watrous, J.; Roach, P.; Alexandrov, T.; Heath, B. S.; Yang, J. Y.;
Kersten, R. D.; van der Voort, M.; Pogliano, K.; Gross, H.;
Raaijmakers, J. M.; Moore, B. S.; Laskin, J.; Bandeira, N.;
Dorrestein, P. C. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, E1743.
(22) von Reuss, S. H.; Bose, N.; Srinivasan, J.; Yim, J. J.; Judkins, J.
C.; Sternberg, P. W.; Schroeder, F. C. J. Am. Chem. Soc. 2012, 134,
1817.
Present Address
⊥(P.E.) Department of Fundamental Microbiology, University
of Lausanne, Lausanne, Switzerland
Notes
The authors declare no competing financial interest.
(23) Bian, X.; Fu, J.; Plaza, A.; Herrmann, J.; Pistorius, D.; Stewart, A.
F.; Zhang, Y.; Muller, R. ChemBioChem 2013, 14, 1194.
(24) Magnuson, K.; Jackowski, S.; Rock, C. O.; Cronan, J. E., Jr.
Microbiol. Rev. 1993, 57, 522.
ACKNOWLEDGMENTS
■
This work was supported by the National Institutes of Health
(1DP2CA186575) and the Damon Runyon Cancer Research
Foundation (DFS:05-12) to J.M.C. We thank Prof. Eric Oswald
(Inserm, France) for providing plasmid pBAC-empty and
pBAC clb+. Binding, Ki determinations, and antagonist
functional data for CNS receptors, transporters, and channels
were generously provided by the National Institute of Mental
Health’s Psychoactive Drug Screening Program (NIMH PDSP
contract no. HHSN-271-2008-00025-C).
(25) Reimer, D.; Pos, K. M.; Thines, M.; Grun, P.; Bode, H. B. Nat.
̈
Chem. Biol. 2011, 7, 888.
(26) Kevany, B. M.; Rasko, D. A.; Thomas, M. G. Appl. Environ.
Microbiol. 2009, 75, 1144.
(27) Xu, Y.; Kersten, R. D.; Nam, S. J.; Lu, L.; Al-Suwailem, A. M.;
Zheng, H.; Fenical, W.; Dorrestein, P. C.; Moore, B. S.; Qian, P. Y. J.
Am. Chem. Soc. 2012, 134, 8625.
(28) Miller, D. A.; Luo, L.; Hillson, N.; Keating, T. A.; Walsh, C. T.
Chem. Biol. 2002, 9, 333.
(29) McKellar, R. C.; Paquet, A.; Ma, C. Y. Food Microbiol. 1992, 9,
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