Hybrid anthracyclines from a genetically engineered Streptomyces galilaeus mutant.
The genetic engineering of antibiotic-producing Streptomyces strains is an approach that is emerging and ready to become established as a successful methodology in developing analogues of the original, pharmaceutically important, natural products obtained from the organisms. The current report highlights this succes by demonstrating the high-level production of novel anthracyclines. The biosynthetic pathways of the nogalamycin-producing Streptomyces nogalater and the aclacinomycin-producing S. galilaeus were combined by transferring the genes of S. nogalater polyketide synthetase into a nonproducing S. galilaeus mutant. The resulting anthracycline antibiotics that were produced possessed structural features characteristic of compounds from both of the undoctored Streptomycesstrains.
Kunnari
T J
TJ
Galilaeus Oy, P.O. Box 113, 20781 Kaarina, Finland, Department of Biochemistry, University of Turku, 20014 Turku, Finland.
Ylihonko
K P
KP
Klika
K D
KD
Mäntsälä
P I
PI
Hakala
J M
JM
D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D002240:Carbohydrate Sequence; D005285:Fermentation; D005818:Genetic Engineering; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics*
D000903:Antibiotics, Antineoplastic