AUTHOR=Forget Stephanie M. , McVey Jennifer , Vining Leo C. , Jakeman David L. 

TITLE=Streptomyces venezuelae ISP5230 Maintains Excretion of Jadomycin upon Disruption of the MFS Transporter JadL Located within the Natural Product Biosynthetic Gene Cluster

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00432

DOI=10.3389/fmicb.2017.00432

ISSN=1664-302X

ABSTRACT=<p>JadL was identified as a Major Facilitator Superfamily (MFS) transporter (T.C. 2.A.1) through sequence homology. The protein is encoded by <italic>jadL</italic>, 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 by <italic>Streptomyces venezuelae</italic> ISP5230. Herein, we evaluate this assumption through the construction and analysis of a <italic>jadL</italic> disrupted mutant, <italic>S. venezuelae</italic> VS678 <italic>(</italic>Δ<italic>jadL::aac(3)IV)</italic>. Quantitative determination of jadomycin production with the <italic>jadL</italic> disrupted 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 of <italic>jadL</italic>, or that JadL is not involved in jadomycin efflux. Potentially, other transporters within <italic>S. venezuelae</italic> ISP5230 may adopt this role upon inactivation of JadL to export jadomycins.</p>