Further studies on the biosynthesis of the manumycin-type antibiotic, asukamycin, and the chemical synthesis of protoasukamycin.
Asukamycin (2), a metabolite of Streptomyces nodosus ssp. asukaensis ATCC 29757 and a member of the manumycin family of antibiotics, is assembled from three components, an "upper" polyketide chain initiated by cyclohexanecarboxylic acid, a "lower" polyketide chain initiated by the novel starter unit, 3-amino-4-hydroxybenzoic acid (3,4-AHBA), and a cyclized 5-aminolevulinic acid moiety, 2-amino-3-hydroxycyclopent-2-enone (C(5)N unit). To shed light on the order in which these components are assembled, we synthesized in labeled form various potential intermediates and evaluated their incorporation into 2. The assembly of the molecular framework of 2 from 3,4-AHBA and cyclohexanecarboxylic acid apparently does not involve free, unactivated intermediates. However, protoasukamycin (12), the total synthesis of which is reported, was efficiently converted into 2, demonstrating that the modification of the aromatic ring to the epoxyquinol structure is the terminal step in the biosynthesis. The results suggest that the two polyketide chains are synthesized separately and that the "upper" chain must be connected to the "lower" polyketide chain before the C(5)N unit.
Hu
Yiding
Y
Department of Chemistry, University of Washington, Box 351700, Seattle, Washington 98195-1700, USA.
Floss
Heinz G
HG
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011090:Polyenes / Q000138:chemical synthesis* / Q000737:chemistry*; D053284:Polyunsaturated Alkamides; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D011090:Polyenes; D053284:Polyunsaturated Alkamides; C013404:asukamycin; C054474:manumycin