3-amino-5-hydroxybenzoic acid in antibiotic biosynthesis. XI. Biological origins and semisynthesis of thionaphthomycins, and the structures of naphthomycins I and J.
Fermentations of Streptomyces sp. E/784 produce low levels of the novel C-30 alkylthio-substituted ansamycin antibiotics naphthomycins J (9) and I (10), in addition to the more abundant C-30 hydroxylated analogues actamycin (1) and naphthomycin D (2) and C-30 chlorinated analogues naphthomycins H (3) and A (4). The addition of N-acetyl-L-cysteine to the fermentation medium substantially increases the production of the thionaphthomycins J and I at the expense of their chloro analogues H and A. Other thiols and thiol progenitors are similarly utilised, including N-acetyl-L-cysteine methyl ester which affords the known naphthomycin F (8) and its novel 2-demethyl homologue (7). The formation of thioansamycins from chloroansamycins and thiols in vivo is probably non-enzymic since similar conversions can be effected in vitro.
Hooper
A M
AM
Research School of Chemistry, Australian National University, Canberra, A.C.T.
Rickards
R W
RW
D000111:Acetylcysteine / Q000378:metabolism; D062365:Aminobenzoates / Q000378:metabolism*; D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005285:Fermentation; D062385:Hydroxybenzoates; D047029:Lactams, Macrocyclic; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*
D062365:Aminobenzoates; D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D062385:Hydroxybenzoates; D047029:Lactams, Macrocyclic; D009285:Naphthoquinones; C115622:naphthomycin I; C115623:naphthomycin J; C010252:naphthomycin; C039870:actamycin; C031509:3-amino-5-hydroxybenzoic acid; D000111:Acetylcysteine