title: Isolation of endophytic bacteria producing the anti-cancer alkaloid camptothecine from Miquelia dentata Bedd. (Icacinaceae).
abstract: Camptothecine (CPT), a quinoline alkaloid, is a potent inhibitor of eukaryotic topoisomerase I. Because of this activity, several semi-synthetic derivatives of CPT are in clinical use against ovarian and small lung cancers. Together with its derivatives, CPT is the third largest anti-cancer drug in the world market. CPT is produced by several plant species belonging to the Asterid clade. In the recent past, several studies have reported the production of CPT by endophytic fungal associates of some of these plant species. In this paper, we report the production of CPT by endophytic bacteria isolated from Miquelia dentata Bedd. (Icacinaceae). Besides CPT, the bacteria also produced 9-methoxy CPT (9-MeO-CPT), in culture, independent of the host tissue. The chemical nature of CPT and 9-MeO-CPT was determined by LC-MS and ESI-MS/MS analysis, and was shown to be similar to that produced by the host tissue. One of the bacterial isolates examined, showed indications of attenuation of CPT production through sub-culture. This is the first report of production of CPT by endophytic bacteria. The identity of the bacteria was ascertained by Gram staining and 16s rRNA sequencing. We discuss the possible mechanisms that might be involved in the synthesis of CPT by endophytic bacteria.
authors.affiliation: School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, Karnataka, India.
authors.forename: S
authors.initials: S
authors.lastname: Shweta
authors.forename: J Hima
authors.initials: JH
authors.lastname: Bindu
authors.forename: J
authors.initials: J
authors.lastname: Raghu
authors.forename: H K
authors.initials: HK
authors.lastname: Suma
authors.forename: B L
authors.initials: BL
authors.lastname: Manjunatha
authors.forename: P Mohana
authors.initials: PM
authors.lastname: Kumara
authors.forename: G
authors.initials: G
authors.lastname: Ravikanth
authors.forename: K N
authors.initials: KN
authors.lastname: Nataraja
authors.forename: K N
authors.initials: KN
authors.lastname: Ganeshaiah
authors.forename: R
authors.initials: R
authors.lastname: Uma Shaanker
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis*; D002166:Camptothecin / Q000096:biosynthesis* / Q000302:isolation & purification; D060026:Endophytes / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D019684:Magnoliopsida / Q000382:microbiology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin
keywords: Alkaloid; Anti-cancer; Camptothecine; Endophytic bacteria; Miquelia dentata; Western Ghats