title: A Rebeccamycin Analog Provides Plasmid-Encoded Niche Defense.
abstract: Bacterial symbionts of fungus-growing ants occupy a highly specialized ecological niche and face the constant existential threat of displacement by another strain of ant-adapted bacteria. As part of a systematic study of the small molecules underlying this fraternal competition, we discovered an analog of the antitumor agent rebeccamycin, a member of the increasingly important indolocarbazole family. While several gene clusters consistent with this molecule's newly reported modification had previously been identified in metagenomic studies, the metabolite itself has been cryptic. The biosynthetic gene cluster for 9-methoxyrebeccamycin is encoded on a plasmid in a manner reminiscent of plasmid-derived peptide antimicrobials that commonly mediate antagonism among closely related Gram-negative bacteria.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Ave., Boston, Massachusetts 02115, United States.
authors.forename: Ethan B
authors.initials: EB
authors.lastname: Van Arnam
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Ave., Boston, Massachusetts 02115, United States.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Ruzzini
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Ave., Boston, Massachusetts 02115, United States.
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Sit
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison , 1550 Linden Dr., Madison, Wisconsin 53706, United States.
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Currie
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Ave., Boston, Massachusetts 02115, United States.
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
mesh_terms: D039903:Actinobacteria / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002227:Carbazoles; C053339:rebeccamycin