Microbial transformation of aklanonic acid, a potential early intermediate in the biosynthesis of anthracyclines.
Sir: Recently, we isolated a new pigment from fermentations of Streptomyces sp. ZIMET 43717". The close structural relationship of this compound (aklanonic acid, Ia, Fig. 1) to anthracyclinones induced us to attempt its biotransformation to anthracyclines by daunorubicin-negative mutants derived from different daunorubicin producing organisms. The results of our experiments provided evidence that aklanonic acid very probably is an early intermediate in the biosynthetic pathway of anthracyclines. Thus, aklanonic acid, its methyl ester, and aklanone, a chemical conversion product of aklanonic acid (Fig. 1)", were fed to fermentations of the mutant strains O3P; and IP,. Both mutant strains were isolated after N-methyl-N'nitro-N'-nitrosoguanidine treatment of daunorubicin-producing Streptomyces griseaus strains. Strain O1P; was derived from IMET JA 5142. Strain IP, is a negative mutant of strain 1P which produces a mixture of new red and blue pigments"'. The chemical structures of the two main red components designated 1P/I and IP/II3) are shown in Fig. 1. Fermentations of the strains O1P; and 1P, were carried out as described2) in 500-m1 flasks each containing 80 ml of medium for 24 hours. Then 3 ml of a solution of substrate in methanol (1 mg/ml) were added to each flask and cultivation continued for 24 hours. Extracts of mycelium with acetone and chloroform (1: 1) were purified by chromatography on KH2PO4 buffered silica gel (chloroform acetone, 10: 2). Identification of the biotransformation products was performed as indicated in Table 1. Glycosides extracted from the culture filtrate were hydrolyzed with 0.1 N HCI. Compound IP/II was purified by column chromatography on silica gel with benzene. The results are listed in Table 1. Aklanonic acid as well as its methyl ester were transformed by mutant O,P, to give e-rhodomycinone, 7deoxy-e-rhodomycinone and glycosides of dauno-
Leukaemomycin‐geblockte Mutanten des Streptomyces griseus und ihre Pigmente II. Neue 7‐Hydroxy‐bisanhydro‐rhodomycinone aus der Mutante ZIMET 41707/1P
Various blocked mutants were isolated from three leukaemomycin-(daunomycin-)producing strains IMET JA 3933, IMET JA 5142 and IMET JA 5570 of Streptomyces griseus by NTG and UV treatments. Among them, one class of four mutants ZIMET 43707/1P, IMET JA 5570/3P, IMET JA 5570/10P and IMET JA 5142/01P1 produced new blue and red pigments. Two red compounds designated 1PI and 1PII are the main components of the pigment complex produced by culture of the blocked mutant ZIMET 43707/1P. This paper describes the isolation of 1PI and IPII; furthermore, the spectral and physicochemical properties of these anthracyclinones and the elucidation of their structures are reported.
MICROBIAL CONVERSION OF ε-PYRROMYCINONE AND ε-ISORHODOMYCINONE TO 1-HYDROXY-13-DIHYDRODAUNOMYCIN AND N-FORMYL-1-HYDROXY-13-DIHYDRODAUNOMYCIN AND THEIR BIOACTIVITIES
New anthracycline antibiotics, 1-hydroxy-13-dihydrodaunomycin and N-formyl-1-hydroxy-13-dihydrodaunomycin were biosynthesized by a blocked mutant of Streptomyces coeruleorubidus MEt30-A4 from e-pyrromycinone or e-isorhodomycinone.