Stoffwechselprodukte von Mikroorganismen, 182. Aufklärung der Struktur des Nucleosidantibiotikums Nikkomycin X

Hagenmaier, Hanspaul; Keckeisen, Adelinde; Zähner, Hans; König, Wilfried Α.

doi:10.1002/jlac.197919791007

Cited by 70 publications

(13 citation statements)

References 6 publications

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“…tendae TuÈ 901 synthesizes pairs of isomeric nikkomycins that dier in the base that is N-glycosidically linked to an aminohexuronic acid, which together form the nucleoside moiety (Hagenmaier et al 1979). 4-Formyl-4-imidazolin-2-one is the base in nikkomycins of the X series, and uracil is present in nikkomycins of the Z series (see below).…”

Section: Introductionmentioning

confidence: 98%

Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin

et al. 2001

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Six genes (nikP1, nikP2, nikS, nikT, nikU, and nikV) from Streptomyces tendae Tu901 were identified by analysis of the nucleotide sequence of the nikkomycin gene cluster. These genes, together with the previously described nikQ and nikR, span 9.39 kb and are transcribed as a polycistronic mRNA in a growth-phase-dependent manner. The nikP1 gene encodes a non-ribosomal peptide synthase consisting of an adenylation domain, a thiolation domain, and an N-terminal 70-residue segment of unknown function. The amino acid sequence encoded by the nikP2 gene displays similarity to the sequences of thioesterases, and the nikS product belongs to a superfamily of proteins characterized by a specific ATP-binding fold. The N-terminal 70 amino acids of the predicted nikT gene product show significant sequence similarity to acyl carrier proteins, and the C-terminal 330 amino acids to aminotransferases. The sequences of the deduced proteins NikU and NikV exhibit similarity to components S and E, respectively, of glutamate mutase from Clostridium. Disruption of the nikP1, nikS, nikT, or nikV gene by insertion of a kanamycin resistance cassette abolished formation of nikkomycins I, J, X, and Z, all of which contain hydroxypyridylhomothreonine as the peptidyl moiety. The nikP1 mutants, and the nikS and nikT mutants accumulated the nucleoside moieties nikkomycin Cz, and nikkomycins Cx and Cz, respectively. The nikV mutants formed nikkomycins Ox and Oz, which contain 2-amino-4-hydroxy-4-(3'-hydroxy-6'-pyridyl) butanoic acid as the peptidyl moiety. The nikP2 mutants synthesized nikkomycins I, J, X, and Z, but amounts of nikkomycins I and X, which contain formylimidazolone as the base, were lower. Feeding formylimidazolone to nikP2 mutants restored the ability to form nikkomycins I and X. Our results indicate that nikU and nikV are required for the synthesis of hydroxypyridylhomothreonine, the genes nikP1, nikP2 and nikS are required for the assembly of nikkomycins, and nikT is required for both pathways. The putative activities of each of their products are discussed.

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Section: Introductionmentioning

confidence: 98%

Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin

et al. 2001

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“…Chitin is a major structural component of the cell walls of many fungi; inhibitors of chitin synthetase, such as the polyoxins (12,13) and nikkomycins (7,9), have been found to hinder fungal growth, although in some cases at much higher concentrations than those effective at the enzymatic level (2,10).…”

mentioning

confidence: 99%

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins

Cabib

1991

Antimicrob Agents Chemother

133

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Polyoxin D, nikkomycin X, and nikkomycin Z are all competitive inhibitors of chitin synthetase 2 (Chs2), the essential enzyme for primary septum formation in Saccharomyces cerevisiae, and of Chs1, a repair enzyme. However, Chs2 is more resistant to these antibiotics than Chs1. When Co2+, the best stimulator of Chs2, was used in the assay for this enzyme, the differences in the Ki values for nikkomycins between the two isozymes reached 3 orders of magnitude. These results point to differences in the active sites of the two isozymes. Polyoxin D was much more effective than nikkomycin Z in inhibiting cell growth. This underlines the importance of the choice of enzyme and of assay conditions when cell wall-synthesizing enzymes are used in screens for possible antifungal agents.

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“…It is interesting to note that a positional isomer of 3c having an aldehyde function at C-4 is an aglycone of the naturally occurring antibiotic nikkomycin X (16).…”

Section: Identification Of Photoproducts 2ac and 3acmentioning

confidence: 99%

Photochemistry of N-(pyrimidin-2-one-4-yl)pyridinium derivatives. The ring contraction of pyrimidinone into imidazolinone

Wenska¹,

Skalski²,

Paszỳc³

et al. 1995

Can. J. Chem.

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Abstract:Photochemical reactions (A > 300 nm) of N-(1-methylpyrimidin-2-one)-and N-(1,Sdimethylpyrimidin-2-0ne)pyridinium chlorides were studied in deoxygenated aqueous solution at various pH's. Only the former compound was found to be reactive under these conditions to give pyrimidine ring contraction photoproducts 1-methyl-4-imidazolin-2-one and 1 -methyl-4-imidazolin-2-one-5-carboxyaldehyde, with pH-dependent chemical yields. The photochemical pyrimidine ring contraction reaction does not occur for other photochemically reactive pyrimidin-2-ones bearing 3-methylimidazolium-l , 1,2,4-triazol-1 -y I, or imidazol-1-yl as substituents at the C-4 position. The suggested mechanism of the reaction involves the addition of water to the pyrimidinone part of the N-(1-methylpyrimidin-2-one)pyridinium salt in the excited triplet state as the primary photochemical step. Addition of alcohol to the pyridinium ring was found to be the major reaction under irradiation of N-(1-methylpyrimidin-2-one-4-y1)pyridinium chloride in methanol.Key words: photochemistry, N-(pyrimidin-2-one-4-y1)pyridinium compounds, pyrimidine ring contraction, 1-substituted-4-imidazolin-2-ones, 4-imidazolin-2-one-5-carboxyaldehydes.RCsumC : Operant j. divers pH, dans des solutions dCsoxygCnCes, on a CtudiC les reactions photochimiques (A > 300 nm) des chlorures de N-(1-mkthylpyrimidin-2-one)-et de N-(l,5-dimethylpyrimidin-2-one)pyridinium. On a trouve que, dans ces conditions, le premier compose est le seul h fournir des photoproduits resultant d'une contraction du noyau pyrimidine, soit la 1 -methyl-4-imidazolin-2-one et le 1-methyl-4-imidazolin-2-one 5-carboxyaldChyde avec des rendements qui varient avec le pH. La reaction photochimique de contraction du noyau pyrimidine ne se produit pas avec les autres pyrimidin-2-ones photochimiquement reactives portant des substituants 3-mCthylimidazolium-l,l,2,4-triazol-1 -yle ou imidazol-1-yle en position C-4. Le mecanisme suggCrC pour la rkaction implique que, dans l'etape photochimique primaire, il y a addition d'eau j. la portion pyrimidinone du sel N-(1-methylpyrimidin-2-0ne)pyridinium dans 1'Ctat excite triplet. Lors de l'irradiation du chlorure de N-(1-mkthylpyrimidin-2-one-4-y1)pyridinium dans le methanol, on observe que l'addition d'alcool est la reaction principale.Mots elks : photochimie, composes N-(pyrimidin-2-one-4-yl)pyridinium, contraction du noyau pyrimidine, 4-imidazolin-2-ones substituCes en position 1,4-imidazolin-2-one-5-carboxaldehydes.[Traduit par la redaction) Common purine and pyrimidine nucleosides such as guanosine, inosine, thymidine, and uridine can be easily and efficiently converted to the corresponding, fluorescent N-(purin-6-y1)-and N-(pyrimidin-2-one-4-y1)pyridinium chlorides (1). Some of these derivatives can be incorporated into synthetic

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Stoffwechselprodukte von Mikroorganismen, 182. Aufklärung der Struktur des Nucleosidantibiotikums Nikkomycin X

Cited by 70 publications

References 6 publications

Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin

Molecular characterization of co-transcribed genes from Streptomyces tendae Tü901 involved in the biosynthesis of the peptidyl moiety and assembly of the peptidyl nucleoside antibiotic nikkomycin

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins

Photochemistry of N-(pyrimidin-2-one-4-yl)pyridinium derivatives. The ring contraction of pyrimidinone into imidazolinone

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