Griseochelin, a novel carboxylic acid antibiotic from Streptomyces griseus.

Abstract

Griseochelin, C3,H;;QO" isolated from an asporogenous strain of Streptonryces griseus represents a novel carboxylic acid antibiotic. The metabolite, which is active against Grarnpositive bacteria, forms water-insoluble salts with mono-and divalent cations and binds alkaline-earth metal ions specifically in 2: 1 (X_M) stoichiometry.Detailed spectral (IR, MS and NMR) studies provide full characterization of its constitution featuring a carboxylic acid function, a substituted tetrahydropyran ring, an allylic OH group which are accomodated within a tetrahydroxylated-octamethyl-C" diene backbone.Griseochelin was isolated in the course of our investigations into the biochemistry of streptomycinnon-producing Amy-mutants derived from high-yielding streptomycin-producing strains of Strepto- StrainThe griseochelin-producing strain, S. griseus ZIMET 43681, was taken from the strain collection of the Central Institute of Microbiology and Experimental Therapy, Jena. It represents a stable prototropic Amy-Str-mutant of the high-yielding, streptomycin-producing (Amy+ Str+) S. griseus HP strain". Derived from the parent strain via glycerol-limited chemostat cultivation, this mutant exhibits a number of modified biochemical properties. In particular, it excels in its capability to produce griseochelin under submerged cultivation in enhanced yields that may exceed those of the parent strain by a factor of 10 to 303). FermentationLyophilized stock mycelia" were first propagated in agar slant cultures at 27°C for 8 days. The medium consisted of baker's yeast 1.5 %, maize starch 1 %, NaCI 0.5 %, peptone (Difco 0.1 %) and agar 2Y. and had a pH 7.0. Samples of the slant cultures were then used to inoculate the growth medium

Preparation of THP‐Ester‐Derived Pyridinium‐Type Salts and their Reactions with Various Nucleophiles

“…) 1d. Typical methods to construct these types of substituted frameworks use nucleophilic‐substitution reactions at the anomeric position (2‐position) of THP ethers or esters.…”

Chemische Synthesen und chemische Biologie von Carboxylpolyether‐Ionophoren: Aktuelle Entwicklungen

“…[38][39][40] Zincophorin weist potente Aktivitätg egen Grampositive Bakterien einschließlich dem hçchst pathogenen Clostridium coelchii auf; [38,40] das Methylester-Derivat zeigt antivirale Aktivitätm itsamt reduzierter Toxizität. [38][39][40] Zincophorin weist potente Aktivitätg egen Grampositive Bakterien einschließlich dem hçchst pathogenen Clostridium coelchii auf; [38,40] das Methylester-Derivat zeigt antivirale Aktivitätm itsamt reduzierter Toxizität.…”

“…Zincophorin Zincophorin (3)-das früher Griseochelin genannt wurde, wobei der aktuelle Name durch die hohe Affinitätd es Moleküls zu Zink-Kationen zustande kommt -w urde 1984 aus Streptomyces griseus isoliert und die Struktur wurde zweifelsfrei über 2D-NMR-und XRD-Untersuchungen aufgeklärt. [38][39][40] Zincophorin weist potente Aktivitätg egen Grampositive Bakterien einschließlich dem hçchst pathogenen Clostridium coelchii auf; [38,40] das Methylester-Derivat zeigt antivirale Aktivitätm itsamt reduzierter Toxizität. [41] Diese potente Aktivitätm acht sowohl Zincophorin als auch den Methylester 4 zu attraktiven Zielmolekülen.…”

Challenges in the synthesis of a unique mono-carboxylic acid antibiotic, (+)-zincophorin

“…In 1984, Gräfe et al reported the isolation of a new mono-carboxylic acid ionophore, griseocholin, from cultured strains of Streptomyces griseus 2. The structure was established first by extensive NMR experiments 3.…”