title: Jadomycins derived from the assimilation and incorporation of norvaline and norleucine.
abstract: Streptomyces venezuelae ISP5230 is recognized for the production of chloramphenicol and the jadomycin family of natural products. The jadomycins are angucycline natural products containing a unique oxazolone ring incorporating an amino acid present in the minimal culture media. Substitution of different amino acids results in products of varying biological activity. Analysis of cultures of S. venezuelae ISP5230 incubated with l- and d-norvaline and l- and d-norleucine indicated that only the d-configured amino acids were incorporated into the natural products. Subsequently, jadomycin DNV and jadomycin DNL were isolated and characterized (titers 4 and 9 mg L(-1), respectively). The compounds were evaluated in the National Cancer Institute cell line cancer growth inhibition and cytotoxicity screens, for antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and as DNA-cleavage agents in vitro.
authors: Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors: Stephanie N
authors: SN
authors: Dupuis
authors: Thomas
authors: T
authors: Veinot
authors: Susan M A
authors: SM
authors: Monro
authors: Susan E
authors: SE
authors: Douglas
authors: Raymond T
authors: RT
authors: Syvitski
authors: Kerry B
authors: KB
authors: Goralski
authors: Sherri A
authors: SA
authors: McFarland
authors: David L
authors: DL
authors: Jakeman
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D002701:Chloramphenicol / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009646:Norleucine / Q000737:chemistry / Q000378:metabolism*; D010081:Oxazolone / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007546:Isoquinolines; C081750:jadomycin B; D010081:Oxazolone; D002701:Chloramphenicol; D009646:Norleucine; D004247:DNA; C005313:norvaline; D014633:Valine