title: Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Streptomyces roseosporus.
abstract: Here, we described the discovery of anti-infective agent arylomycin and its biosynthetic gene cluster in an industrial daptomycin producing strain Streptomyces roseosporus. This was accomplished via the use of MALDI imaging mass spectrometry (IMS) along with peptidogenomic approach in which we have expanded to short sequence tagging (SST) described herein. Using IMS, we observed that prior to the production of daptomycin, a cluster of ions (1-3) was produced by S. roseosporus and correlated well with the decreased staphylococcal cell growth. With a further adopted SST peptidogenomics approach, which relies on the generation of sequence tags from tandem mass spectrometric data and query against genomes to identify the biosynthetic genes, we were able to identify these three molecules (1-3) to arylomycins, a class of broad-spectrum antibiotics that target type I signal peptidase. The gene cluster was then identified. This highlights the strength of IMS and MS guided genome mining approaches in effectively bridging the gap between phenotypes, chemotypes, and genotypes.
authors: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, Unites States.
authors: Wei-Ting
authors: WT
authors: Liu
authors: Roland D
authors: RD
authors: Kersten
authors: Yu-Liang
authors: YL
authors: Yang
authors: Bradley S
authors: BS
authors: Moore
authors: Pieter C
authors: PC
authors: Dorrestein
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D030562:Databases, Protein; D016680:Genome, Bacterial / Q000235:genetics*; D015394:Molecular Structure; D009842:Oligopeptides / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013302:Streptomyces / Q000166:cytology / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides