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-
Biosynthesis of anthracyclinones: isolation of a new early cyclization product aklaviketone.
Five metabolites were isolated from fermentations of a mutant strain S 383 of Streptomyces galilaeus. Components S 383-O and S 383-A were identified as known derivatives of anthraquinone and naphthacenequinone, respectively, previously isolated from cultures of other blocked mutants of S. galilaeus strains. Component S 383-X was identical with 7-deoxyaklavinone. Compound S 383-Y (aklaviketone) was found to be a new metabolite. Its chemical structure has been determined by physico-chemical methods including mass spectrometry and NMR spectral studies. The compound (7-dehydro-7-deoxy-7-oxoaklavinone) is most likely the first cyclization product along the metabolic chain possessing the tetracyclic carbon skeleton of anthracyclinones. A proposed pathway is discussed.
The Gospel and the land;: Early Christianity and Jewish territorial doctrine,
Ostensibly Davies' patient study of the concepton of the "land" (Israel, Jerusalem) in early Christianity is an essay in Biblical theology, but he also wishes to raise serious questions about Christian understanding (or misunderstanding) of Judaism. "Christians have usually understood Judaism in too theological, and therefore, too intellectual terms. And they have also looked at their own foundation document, the New Testament, in the same way. In their proper concern to unravel theological developments and subtleties in primitive Christianity, they have neglfected to search for evidences of an encounter between it and the realia of Judaism and for any possible resolutions of such an tencounter. In particular, they have failed to inquire after the place of the land in the thought and lives of early Christians" (p. 161). Davies observes, for example, that bible dictionaries often have no references whatsoever to "land" and those that do allot it but a few pages. Even in Old Testament scholarship, where the land is of central significance in the documents themselves, it has been neglected. His work is an attempt to provide a context of Jewish thinking from early Israelite writings up to the Talmud in which to place the Christian materials. The bulk of the book is an account of the historical and theological process by which early Christianity gave a "spiritual" interpretation of traditional Jewish views of the land. Read against the Jewish background, the radical spiritualizing of the tradition is striking. Yet Davies also shows that Jewish attitudes were not monolithic in the first century, that notions of a preexistent, heavenly or eschatological Jerusalem were present, and that some Jews considered the viability of Judaism apart from the land. At some point however what could be entertained as an abstraction in Judaism, when it was made concrete in the life of the Christian movement, could not be tolerated. The conflict was heightened, of course, by the destruction of Jerusalem and the continued existence of Christianity as a movement increasingly receptive to non-Jews. Christianity, however, while rejecting the link between the land and religion, did create a new sense of "holy space" by hallowing the places where Christ had been, a development which would find fullest expression some several centuries later. As a result of the Holocaust and the establishment of the modern state of Israel Christians are faced with a whole new series of issues which have lain dormant since the destruction of Jerusalem in A.D. 70. Davies' work must be read against this backdrop to appreciate its significance. It is as much a book about modern Christian thinking as it is about the past, as many of his citations and his several appendices of speeches at Jewish-Christian conferences show. To some it may appear that he has sided too closely with certain strands of Judaism and allowed this to color his way of handling the pre-Christian and pre-Rabbinic material, but such criticism is carping. Much of the material here is gathered together in this fashion for the first time, and he has successfully shown that a major preoccupation of ancient Judaism is missing in contemporary biblical scholarship. Further, he has given us a moving yet scholarly statement of the pathos of the modern Christian who cares about Christ and Israel and who tries to understand Israel while loving Christ.