Use of D-[13C6]glucose together with carbon-13-depleted glucose and homonuclear carbon-13 decoupling to identify the labeling pattern by this precursor of the "m-C7N" unit of geldanamycin

Rinehart, Kenneth L.; Potgieter, M.; Wright, David

doi:10.1021/ja00373a059

Cited by 30 publications

(11 citation statements)

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“…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 …”

supporting

confidence: 60%

“…Thus the formation of 2 must branch ~, off from the miin pathway at an earlier stage. Another intriguing feature is the finding, in the cases of the mitomycins (37) geldanamycin (15) and ansatrienin A (38), that the nitrogen atom of the mC7N unit is attached to the carbon atom corresponding to C5, not C3, of a shikimate-equivalent moiety. The same conclusion is reached about the mC7N unit of 1 from the results of the [~-'~~~]~l~c e r o l experiment presented above.…”

Section: Resultsmentioning

confidence: 99%

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Biosynthesis of naphthomycin A in Streptomyces collinus

Lee¹,

Tsao²,

Chang³

et al. 1994

Can. J. Chem.

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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...

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supporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Biosynthesis of naphthomycin A in Streptomyces collinus

Lee¹,

Tsao²,

Chang³

et al. 1994

Can. J. Chem.

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“…Degradations of mitomycins derived from various labeled precursors indicated that the C-5-equivalent carbon carries the nitrogen. 21 Although this result was initially questioned when it was found that in pactamycin the C-3-equivalent carbon carries the nitrogen, 15 this turned out to be an anomaly, and further work by Rinehart et al 40 on geldanamycin soon confirmed Hornemann's conclusion from the mitomycin study. Subsequent work in other systems also confirmed the site of attachment of the nitrogen.…”

Section: Historymentioning

confidence: 99%

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

2010

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The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.

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“…Gabaculine (5-amino-1,3-cyclohexadienelcarboxylic acid), a naturally occurring amino acid isolated from Streptomyces toyocaenis (56), is an irreversible inhibitor of many PLP-requiring aminotransferases (57). Rinehart et al (58) and Ganem (59) had, in fact, suggested that this compound might be an intermediate on the biosynthetic pathway to mC 7 N units. In view of the structural similarity of gabaculine and aminoDHS, we checked the effect of gabaculine on AHBA synthase.…”

Section: -Amino-5-hydroxybenzoic Acid Synthasementioning

confidence: 99%

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

Kim

Fryhle

et al. 1998

Journal of Biological Chemistry

112

116

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The biosynthesis of ansamycin antibiotics, like rifamycin B, involves formation of 3-amino-5-hydroxybenzoic acid (AHBA) by a novel variant of the shikimate pathway. AHBA then serves as the starter unit for the assembly of a polyketide which eventually links back to the amino group of AHBA to form the macrolactam ring. The terminal enzyme of AHBA formation, which catalyzes the aromatization of 5-deoxy-5-amino-3-dehydroshikimic acid, has been purified to homogeneity from Amycolatopsis mediterranei, the encoding gene has been cloned, sequenced, and overexpressed in Escherichia coli. The recombinant enzyme, a (His) 6 fusion protein, as well as the native one, are dimers containing one molecule of pyridoxal phosphate per subunit. Mechanistic studies showed that the enzyme-bound pyridoxal phosphate forms a Schiff's base with the amino group of 5-deoxy-5-amino-3-dehydroshikimic acid and catalyzes both an ␣,␤-dehydration and a stereospecific 1,4-enolization of the substrate. Inactivation of the gene encoding AHBA synthase in the A. mediterranei genome results in loss of rifamycin formation; production of the antibiotic is restored when the mutant is supplemented with AHBA.

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Use of D-[13C6]glucose together with carbon-13-depleted glucose and homonuclear carbon-13 decoupling to identify the labeling pattern by this precursor of the "m-C7N" unit of geldanamycin

Cited by 30 publications

References 1 publication

Biosynthesis of naphthomycin A in Streptomyces collinus

Biosynthesis of naphthomycin A in Streptomyces collinus

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

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