title: Streptomyces venezuelaeISP5230 Maintains Excretion of Jadomycin upon Disruption of the MFS Transporter JadL Located within the Natural Product Biosynthetic Gene Cluster.
abstract: JadL was identified as a Major Facilitator Superfamily (MFS) transporter (T.C. 2.A.1) through sequence homology. The protein is encoded byjadL, situated within the jadomycin biosynthetic gene cluster. JadL has, therefore, been assigned a putative role in host defense by exporting its probable substrates, the jadomycins, a family of secondary metabolites produced byStreptomyces venezuelaeISP5230. Herein, we evaluate this assumption through the construction and analysis of ajadLdisrupted mutant,S. venezuelaeVS678(ΔjadL::aac(3)IV). Quantitative determination of jadomycin production with thejadLdisrupted mutant did not show a significant decrease in production in comparison to the wildtype strain, as determined by HPLC and by tandem mass spectrometry. These results suggest that efflux of jadomycin occurs upon disruption ofjadL, or that JadL is not involved in jadomycin efflux. Potentially, other transporters withinS. venezuelaeISP5230 may adopt this role upon inactivation of JadL to export jadomycins.
authors.affiliation: Department of Chemistry, Dalhousie University Halifax, NS, Canada.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Forget
authors.affiliation: Department of Biology, Dalhousie University Halifax, NS, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McVey
authors.affiliation: Department of Biology, Dalhousie University Halifax, NS, Canada.
authors.forename: Leo C
authors.initials: LC
authors.lastname: Vining
authors.affiliation: Department of Chemistry, Dalhousie UniversityHalifax, NS, Canada; College of Pharmacy, Dalhousie UniversityHalifax, NS, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Jakeman
keywords: MFS transporters; drug efflux; jadomycins; major facilitator superfamily; natural products; streptomyces