-
ISOLATION AND IDENTIFICATION OF 4-KETO-5-AMINO-6-HYDROXYHEXANOIC ACID
KATO L. PERLMAN, ULRIKE SCHÖMER, TOM H . WILLIAMS, DAVID PERLMAN
1981 Volume 34 Issue 5 Pages
483-488
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
4-Keto-5-amino-6-hydroxyhexanoic acid was isolated from
Bacillus cereus 102804 fermentations and found to inhibit the growth of Gram-positive and Gram-negative bacteria, when grown in a chem δ-aminolevulinic acid dehydratase. The Ki value of 4-keto-5-amino-6-hydroxyhexanoic acid in an enzyme preparation of
Propionibacterium shermanii was 0.72 μM. Similar test conditions with 4-keto-5-aminohexanoic acid resulted in a Ki of 12.1 μM. In both cases competitive inhibition was found. The structure of 4-keto-5-amino-6-hydroxyhexanoic acid was determined.
View full abstract
-
I. ISOLATION OF THE MUTANT, FERMENTATION AND ANTIMICROBIAL PROPERTIES
SEIICHI TANIDA, MOTOWO IZAWA, TORU HASEGAWA
1981 Volume 34 Issue 5 Pages
489-495
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
A mutant having a high ability to produce ansamitocins was derived from a dnacin-producing strain,
Nocardia sp. No. C-14482 (N-1001), by treatment with ethidium bromide. Mutant N-1231 produced ansamitocins P-3 and P-4 as major components, but was deficient in its ability to produce dnacins. Strain N-1231 also produced fifteen novel ansamitocin analogs as minor components. These analogs showed no activity against prokaryotic microorganisms. The results of determining the activity inhibiting cilia regeneration of deciliated Tetrahymena pyriformis suggest that hydroxylation of C15, C26 and the acyl moiety at C3 of ansamitocins may cause marked reduction of their antitubulinic activities whereas demethylation of -NCH3 at C18 slightly affected their activities.
View full abstract
-
II. ISOLATION AND STRUCTURE
MOTOWO IZAWA, SEIICHI TANIDA, MITSUKO ASAI
1981 Volume 34 Issue 5 Pages
496-506
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
Fifteen new ansamitocin analogs and deacetylmaytanbutacine were isolated from the culture broth of a mutant strain of
Nocardia sp. No. C-14482. Their chemical structures were determined on the basis of spectroscopic and chemical evidence.
View full abstract
-
G. ALBERS-SCHÖNBERG, H. JOSHUA, M. B. LOPEZ, O. D. HENSENS, J. P. ...
1981 Volume 34 Issue 5 Pages
507-512
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
A new, potent hypocholesterolemic agent is produced by cultures of
Aspergillus terreus. The isolation of the compound and its characterization as 4a, 5-dihydromevinolin containing a
trans-fused octahydro-naphthalene system are described. Comparative data for dihydromevinolin and mevinolin in three biological assays are given:
in vitro inhibition of HMG-CoA reductase, inhibition of sterol synthesis in cell cultures, and inhibition of cholesterol synthesis
in vivo in rats.
View full abstract
-
II. SELECTIVE PROTECTION OF FORTIMICINS A AND B
MORIYUKI SATO, KENICHI MOCHIDA, YASUKI MORI, KUNIKATSU SHIRAHATA
1981 Volume 34 Issue 5 Pages
513-521
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
The four amino groups of fortimicin B(
4) could be differentiated from each other and 2'-N-benzyloxycarbonyl-, 2', 6'-di-N-benzyloxycarbonyl-, 2'-N-
tert-butoxycarbonyl-, 6'-N-
tert-butoxycarbonyl- and 2', 6'-di-N-
tert-butoxycarbonyl-fortimicin B (
7, 8, 16, 18, 17) were prepared from
4. From these fortimicin B derivatives, selectively protected fortimicin A derivatives
13, 15, 21, 22 and
25 were prepared by combination of procedures of benzyloxycarbonylation or
tert-butoxycarbonylation, 4-N-glycylation.
View full abstract
-
III. PREPARATION OF N-SUBSTITUTED FORTIMICIN A DERIVATIVES
KENICHI MOCHIDA, MORIYUKI SATO, SHIGEO YOSHIIE, YASUKI MORI, KUNIKATSU ...
1981 Volume 34 Issue 5 Pages
522-529
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
The 1, 2' or 6'-amino group of fortimicin A was alkylated or acylated and the antimicrobial activities of the derivatives were compared with each other. 2'-N-Substituted fortimicins A were active against the fortimicin A resistant strain which produced AAC(3)-I. AAC(3)-I is the only enzyme which can inactivate fortimicin A. Among the derivatives prepared in the present study, 2'-N-[(
S)-4-amino-2-hydroxybutyl]fortimicin A showed stronger activity than fortimicin A. Fortimicins (FM) are pseudodisaccharide aminocyclitol antibiotics produced by Micromonospora
View full abstract
-
IV. PREPARATION OF 4, 2'-DI-N-SUBSTITUTED FORTIMICIN B DERIVATIVES
MORIYUKI SATO, KENICHI MOCHIDA, SHIGEO YOSHIIE, YASUKI MORI, KUNIKATSU ...
1981 Volume 34 Issue 5 Pages
530-535
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
2-Aminoethyl, glycyl, (
S)-4-amino-2-hydroxybutyl and (
S)-4-amino-2-hydroxybutyryl groups were introduced to the 2'-amino group of 4-N-[(
S)-4-amino-2-hydroxybutyl]fortimicin B (
2). All of the derivatives of this type prepared showed antibacterial activity almost as strong as fortimicin A (
1) and were also active against fortimicin A resistant bacteria which can inactivate fortimicin A by producing an inactivating enzyme AAC(3)-I.
View full abstract
-
D. AUTISSIER, P. BARTHELEMY, N. MAZIERES, M. PEYRE, L. PENASSE
1981 Volume 34 Issue 5 Pages
536-543
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
From broths of a neomycin producing
Streptomyces fradiae and of a mutant of
Streptomyces rimosus forma
paromomycinus respectively, 6'''-deamino-6'''-hydroxyneomycin and 6'''-deamino-6'''-hydroxyparomomycin were obtained and their structures established by mass and
13C-NMR spectroscopy and by the study of hydrolytic fragments. These new compounds, which are both present as two epimers at C-5''', are suggested as intermediates in the biosynthesis of the parent antibiotics. The place and the mechanism of the 5'''-epimerisation and of the 6'''-amination are discussed.
View full abstract
-
N. MAZIERES, M. PEYRE, L. PENASSE
1981 Volume 34 Issue 5 Pages
544-550
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
From auxotrophic double mutants of
Streptomyces rimosus forma
paromomycinas and
Streptomyces kanamyceticus producing little or no antibiotic, stable prototrophic recombinants were obtained with low frequencies. Most of the recombinants differed from the parents in morphology and antibiotic production. The most frequent classes of recombinants behaved as streptomycetes of the "red" series and produced a wide range of neomycin yields, in contrast to the parents which produced paromomycin and a small proportion of neomycin, or kanamycin, respectively. Hypotheses on the nature of the genetic material exchanged are discussed.
View full abstract
-
ROLF G. WERNER, ARNOLD L. DEMAIN
1981 Volume 34 Issue 5 Pages
551-554
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
Tryptophan in a concentration of 0.4μg/ml increased the production of indolmycin by 37%. The lipophilic character of indolmycin was reduced
via directed biosynthesis by substituting the aromatic ring system with a methoxy or hydroxy group in the 5-position of the antibiotic. This substitution was achieved by the addition of the corresponding tryptophan and indole precursors to a growing culture of
Streptomyces griseus ATCC 12648. The more hydrophilic indolmycin derivatives displayed a moderate increase in antimicrobial activity as compared to indolmycin, but did not markedly change the Gram-positive/Gram-negative ratio of activity. Thin-layer chromatography and mass spectrometry showed that additives substituted in the 6-position were not incorporated into the molecule. Antibiotic titer was reduced by addition of the modified precursors, especially in the case of the precursors substituted in the 6-position.
View full abstract
-
C. J. CHANG, H. G. FLOSS, D. J. HOOK, J. A. MABE, P. E. MANNI, L. L. M ...
1981 Volume 34 Issue 5 Pages
555-566
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
Feeding experiments with tryptophan samples labeled specifically with radioactive and stable isotopes have shown that
Pseudomonas aureofaciens converts this amino acid into pyrrolnitrin in such a way that the indole nitrogen gives rise to the nitro group, the amino group becomes the pyrrole nitrogen, C-3 of the precursor side chain becomes C-3 of the antibiotic, and H-2 of the indole ring and H-α of the side chain give rise to H-5 and H-2 of pyrrolnitrin, respectively. Only the L-isomer of tryptophan is incorporated with retention of the α-hydrogen and the amino nitrogen. From the D-isomer the labels from these two positions are lost. The obvious conclusion that L-tryptophan is the more immediate precursor is, however, contradicted by the better incorporation of D- than L-tryptophan into the antibiotic. Several potential pathway intermediates were evaluated for incorporation and 4-(
o-aminophenyl)-pyrrole was found to be a good precursor. The results are discussed in terms of a plausible pathway for pyrrolnitrin biosynthesis.
View full abstract
-
H. R. FELIX, H. H. PETER, H. J. TREICHLER
1981 Volume 34 Issue 5 Pages
567-575
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
A mutant of
Cephalosporium acremonium producing high amounts of penicillin N was isolated. This antibiotic was purified and characterized. It was possible to convert this penicillin N to deacetoxycephalosporin C enzymatically. The reaction could be carried out with enzyme systems prepared from
C. acremonium mutants producing either no β-lactam antibiotics or excreting only penicillin N. It was surprising that a high level of transformation capacity was just found in a cephem negative mutant which overproduces penicillin N. For that reason the inability of the latter mutant to produce cephem compounds cannot be explained by a functional block of the ring expanding enzyme complex. The enzyme preparations used to carry out this reaction were made by ether-treatment or sonication of
C. acremonium cells, or by submitting them to osmotic shock. The ring expanding enzyme system is strongly dependent on ATP and behaves as a 2-oxoglutarate dependent dioxygenase.
View full abstract
-
HIROSHI KURAMOCHI, KATSUTOSHI TAKAHASHI, TOMOHISA TAKITA, HAMAO UMEZAW ...
1981 Volume 34 Issue 5 Pages
576-582
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
The base-release activity of oxygen adduct of bleomycin-Fe(II) complex [BLM-Fe(II)] from DNA decreased with a half-life of 5.2 minutes, when incubated at 0°C in 0.05 M Tris-HCl buffer at pH 7.8 in the absence of DNA. Under the same condition, however, visible and ESR spectra showed that the adduct was immediately converted into the ferric complex. The ESR study further indicated the simultaneous formation of two kinds of the low-spin BLM-Fe(III) complex. One of them disappeared in parallel with the decrease of the base-release activity and transformed into the other. The latter Fe(III) complex was stable but inactive. However, by addition of hydrogen peroxide to the latter, the former was regenerated and the base-release activity appeared. Oxygen concentration measurements by oxygraph showed that one mole of BLM-Fe(II) consumed approximately 0.5 mole of molecular oxygen instantly, but did not any more thereafter in the absence of a reducing agent. While in the presence of 2-mercaptoethanol, the oxygen consumption proceeded biphasically, and equimolar oxygen was consumed by BLM-Fe(II) in the first rapid reaction. These results suggest that oxygen adduct of BLM-Fe (II) is reduced by one electron transfer from an external electron donor and the resulting BLM-Fe(III)-O
2H
- [or its deprotonated form: BLM-Fe(III)-O
22-] shows the activity to break DNA accompanying the base-release.
View full abstract
-
BRIAN A. KERN, EDWARD INAMINE
1981 Volume 34 Issue 5 Pages
583-589
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
Extracts of the cephamycin C producer
S. lactamdurans were found to possess cystathionine γ-lyase activity (E.C. 4.4.1.1). This represents the first demonstration of this enzyme of the reverse transsulfuration pathway in a prokaryotic organism. A likely involvement of reverse transsulfuration in antibiotic synthesis is indicated by the fact that propargylglycine, a mechanism-based inhibitor of the γ-lyase, is a strong inhibitor of cephamycin C production.
View full abstract
-
R. B. WRIGHT, S. D. MAKOVER, E. TELEP
1981 Volume 34 Issue 5 Pages
590-595
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
Studies on the binding of Ro 13-9904, a new broad-spectrum cephalosporin, showed that it had higher affinities for PBPs 1b, 2, and 3 of
Escherichia coli (3>1b>2) than cefazolin, cephaloridine, cephalothin or cephalexin. With
Haemophilus influenzae, Ro 13-9904 showed highest affinities for PBPS 4 and 5 followed by PBP 2. It inhibited total cell wall synthesis at lower concentrations than the other β-lactam antibiotics tested.
View full abstract
-
SOICHIRO TODA, SUSUMU NAKAGAWA, TAKAYUKI NAITO, HIROSHI KAWAGUCHI
1981 Volume 34 Issue 5 Pages
596-599
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
S. J. BOX, G. HANSCOMB, S. R. SPEAR
1981 Volume 34 Issue 5 Pages
600-601
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
MOHINDAR S. PUAR
1981 Volume 34 Issue 5 Pages
602-604
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
JEFFREY J. KIBBY, RODNEY W. RICKARDS
1981 Volume 34 Issue 5 Pages
605-607
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
AKIKO FUJIWARA, TATSUO HOSHINO, MASAAKI TAZOE, MITSUHIKO FUJIWARA
1981 Volume 34 Issue 5 Pages
608-610
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
JIRO ITOH, SHOJI OMOTO, TAKASHI SHOMURA, NOBUSUKE NISHIZAWA, SHINJI MI ...
1981 Volume 34 Issue 5 Pages
611-613
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
Y. K. TONY LAM, V. P. GULLO, R. T. GOEGELMAN, D. JORN, L. HUANG, C. DE ...
1981 Volume 34 Issue 5 Pages
614-616
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
NAOHITO TAKEDA, MASAYO UMEMURA, KEN-ICHI HARADA, MAKOTO SUZUKI, AKIRA ...
1981 Volume 34 Issue 5 Pages
617-618
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS
-
M. S. PUAR, B. K. LEE, H. MUNAYYER, R. BRAMBILLA, J. A. WAITZ
1981 Volume 34 Issue 5 Pages
619-620
Published: 1981
Released on J-STAGE: April 12, 2006
JOURNAL
FREE ACCESS