No abstract

Taxol (1) and taxotere have continued to attract considerable attention because of their promise as agents against various types of cancer (Figure 1). While the threat to the original source of taxol, the Pacific yew, has been diminished as new semisynthetic avenues1 to supply (based upon the availability of 10-deacetylbaccatin III from renewable sources2) have been developed, supply and cost are still major issues. It is anticipated that biosynthetic studies might provide insights which could help alleviate these problems.Early work on taxanes, cf.3•4 for example, taxine B (4), showed that there are several natural taxanes in which side chains structurally analogous to the taxol C-13 side chain are esterified to the 5-hydroxyl group of the diterpene moiety. This, together Taxine-B (4)

The biosynthesis of naphthomycin A (1) in Streptonzyces collirt~rs was studied in feeding experiments with single and multiple I3c-labeled precursors followed by I3c NMR analysis of the labeling and I3c-l3c coupling patterns in the product. The results indicate that 1 is assembled via the polyketide pathway from 3-amino-5-hydroxybenzoic acid (2) as the starter unit (mC7N unit) plus seven propionate and six acetate chain extension units. 2 is synthesized via the shikimate pathway by a process that attaches the nitrogen to the carbon derived from C1 of erythrose 4-phosphate, consistent with a new branch of the shikimate pathway recently discovered to operate in the biosynthesis of the mC7N unit of rifamycin B.JONATHAN P. LEE, SHFNG-WAN TSAO, CHING-JER CHANG, XIAN-GUO HE et HBINZ G. FLOSS. Can. J. Chem. 72, 182 (1994).On a CtudiC la biosynthkse de la naphtomycine A (1) dans le Srrepromyces collinus en prockdant B des expkriences au cours desquelles on a foumi des pricurseurs comportant des marqueurs au I3C simples ou multiples alors que l'on a suivi le marquage par une analyse RMN du I3c et par les patrons de couplage I3C-13C dans 1e produit. Les rCsultats indiquent que le produit 1 s'assemble par le biais d'une voie impliquant la formation d'un polycCtide B partir de l'acide 3-amino-5-hydroxybenzoi'que (2) (unit6 mC7N) et des sept unites propioniques et six chaines acCtiques agissant comme extensions. Le composC 2 est synthCtisC par une voie impliquant l'acide shikimique, par un processus que attache un azote au carbone dCrivC du C14-phosphate d'Crythrose; ceci est en accord avec une nouvelle branche de la voie shikimique d6couverte rCcemment et qui est impliquCe dans la biosynthkse de l'unit6 mC7N de la rifamycine B.[Traduit par la rCdaction] Naphthomycin A (I), first isolated from Streptomyces collinus Tii 105 by Balerna et al. (I), is a naphthalenic ansamycin (2, 3) antibiotic that contains an unusually large number of carbon atoms, 23, in its ansa chain. Its constitutional formula was first proposed by Williams (4) and later revised by Rinehart and coworkers (5). The structure was subsequently confirmed by X-ray crystallography, which, together with chemical degradations, also established the absolute configuration (6). Naphthomycin A co-occurs with a number of congeners (1,7,8) and is structurally related to actamycin (8, 9) and the naphthoquinomycins (10). Unlike other ansamycins, 1 is active against Gram-positive bacteria and its mode of action is different from that of other naphthalenic ansamycins, which generally inhibit bacterial RNA polymerase. Its action is antagonized by vitamin K and by sulfhydryl compounds like cysteine (1).In this paper we report the results of studies on the biosynthesis of naphthomycin A that show that its formation probably follows a pathway similar to that previously demonstrated for rifarnycin S (1 1-13), geldanamycin (14, 15), actamycin (9, 16), and ansatrienin (13,17,18 Results and discussionThe origin of the carbon framework of both the naphthoquinoid nucleus and the macr...

Experiments with cerulenin-inhibited cultures of 5. violaceoruber showed conversion of dihydrogranaticin (II) into granaticin (I), but not vice versa, confirming an earlier conclusion that II is the biosynthetic precursor of I. Feeding of CH313C18O2Na followed by 13C-NMR analysis of the product by the 18O shift method indicated the expected incorporation of 18O at carbons 1,11 and 13 of I and showed that the oxygen of the pyran ring originates from C-3 and not from C-15. Analysis of I biosynthesized from 13C2H3COONa by 13C{1H, 2H} triple resonance NMR spectro­scopy showed the incorporation of one atom of deuterium each at C-2 and C-4. C-16 carried a maximum of 2, not 3, atoms of deuterium. These results are discussed in terms of biosynthetic mechanisms.