title: Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029.
abstract: The platensimycin (PTM) and platencin (PTN) class of natural products are promising drug leads that target bacterial and mammalian fatty acid synthases. Natural congeners and synthetic analogues of PTM and PTN have been instrumental in determining their structure-activity relationships, with only a few analogues retaining the potencies of PTM and PTN. Here we describe the identification and isolation of two new sulfur-containing PTM congeners (3 and 5) from the engineered dual PTM-PTN overproducing Streptomyces platensis SB12029. Structure elucidation of platensimycin D1 (5), a sulfur-containing PTM pseudo-dimer, revealed the existence of its presumptive thioacid precursor (3). The unstable thioacid 3 was isolated and confirmed by structural characterization of its permethylated product (6). LC-MS analysis of crude extracts of SB12029 confirmed the presence of the thioacid analogue of PTN (4). The minimum inhibitory concentration (MIC) was determined for 5 revealing retention of the strong antibacterial activity of PTM.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, United States.
authors.forename: Liao-Bin
authors.initials: LB
authors.lastname: Dong
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rudolf
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, United States; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, United States; Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute, Jupiter, FL 33458, United States. Electronic address: shenb@scripps.edu.
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
mesh_terms: D000218:Adamantane / Q000032:analysis / Q000494:pharmacology*; D062365:Aminobenzoates / Q000032:analysis / Q000494:pharmacology*; D000627:Aminophenols / Q000032:analysis / Q000494:pharmacology*; D000813:Anilides / Q000032:analysis / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology*; D001688:Biological Products / Q000032:analysis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects; D011083:Polycyclic Compounds / Q000032:analysis / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry*; D013455:Sulfur / Q000032:analysis / Q000494:pharmacology*
chemical_list: D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D000900:Anti-Bacterial Agents; D001688:Biological Products; D011083:Polycyclic Compounds; D013455:Sulfur; D000218:Adamantane; C510909:platensimycin; C520340:platencin
keywords: Antibacterial; Natural products; Platencin; Platensimycin; Sulfur-containing