J. Jizba

Macrotetrolide antibiotics produced byStreptomyces globisporus

Macrotetrolides isolated from a new producer,Streptomyces globisporus, were identified as nonactin, monactin, dinactin and trinactin. Spectroscopic characterization of these compounds was extended by13NMR spectra. Chemical ionization with ammonia as reactive gas was proposed for mass-spectroscopic characterization of their mixtures. Their biological activity was confirmed by using larvae of the Colorado potato beetle (Leptinotarsa decemlineata) as a new test model.

Biotransformations of anthracyclinones inStreptomyces coeruleorubidus andStreptomyces galilaeus

The ability to transform biologically exogenous daunomycinone, 13-dihydrodaunomycinone, aklavinone, 7-deoxyaklavinone, ε-rhodomycinone, ε-isorhodomycinone and ε-pyrromycinone was studied in submerged cultures of the following strains: wildStreptomyces coeruleorubidus JA 10092 (W1) and its improved variants 39–146 and 84–17 (type P1) producing glycosides of daunomycinone and of 13-dihydro-daunomycinone, together with ε-rhodomycinone, 13-dihydrodaunomycinone and 7-deoxy-13-dihydro-daunomycinone; in five mutant types ofS. coeruleorubidus (A, B, C, D, E) blocked in the biosynthesis of glycosides and differing in the production of free anthracyclinones; in the wildStreptomyces galilaeus JA 3043 (W2) and its improved variant G-167 (P2) producing glycosides of ε-pyrromycinone and of aklavinone together with 7-deoxy and bisanhydro derivatives of both aglycones; in two mutant typesS. galilaeus (F and G) blocked in biosynthesis of glycosides and differing in the occurrence of anthracyclinones. The following bioconversions were observed: daunomycinone → 13-dihydrodaunomycinone and 7-deoxy-13-di-hydrodaunomycinone (all strains); 13-dihydrodaunomycinone → 7-deoxy-13-dihydrodaunomycinone (all strains); daunomyeinone or 13-dihydrodaunomycinone → glycosides of daunomyeinone and of 13-dihydrodaunomycinone, identical with metabolites W1 and P1 (type A), or only a single glycoside of daunomyeinone (type E); aklavinone → ε-rhodomycinone (types A and B); aklavinone → 7-deoxyaklavinone and bisan-hydroaklavinone (type C); ε-rhodomycinone → ζ-rhodomycinone (types C, E); ε-rhodomycinone → glycosides of ε-rhodomycinone (types W2, P2); ε-isorhodomycinone → glycosides of ε-isorhodomycinone (types W2, P2); ε-pyrromycinone → a glycoside of ε-pyrromycinone (types W1, P1). 7-Deoxyaklavinone remained intact in all tests. Exogenous daunomyeinone suppressed the biosynthesis of its own glycosidea in W1 and P1; it simultaneously increased the production of ε-rhodomyeinone in P1.

Insecticidal properties of nonactic acid and homononactic acid, the precursors of macrotetrolide antibiotics

Abstract(±)-Nonactic acid (1) and (±)-homononactic acid (2), the non-antibiotic precursors of macrotetrolide antibiotics, showed significant insecticidal effects (comparable with those of the commercial synthetic pesticide Metathion) onLeptinotarsa decemlineata, Epilachna varivestis andEuproctis chrysorrhoea. Anisoplia austriaca, Aphis fabae andCalandra granaria were less sensitive in this respect. A low acaricidal activity againstTetranychus urticae (not reaching that of the commercial miticide Acarition) was also found. Both1 and2 exhibited growth-stimulating properties for plants.

TLC and HPLC of Mixture of Anthracyclinones

Abstract A combination of TLC and HPLC was used to separate a natural mixture of anthracyclinones /daunomycinone, 7-deoxydaunomycinone, 7-deoxy-13-dihydrodaunomycinone, 13-dihydrodaunomycinone, carminomycinone, 13-dihydrocarminomycinone, “bisanhydrocarminomycinone” and e-rhodomycinone/. The method is suitable for routine analysis of anthracyclinones in the course of their biosynthesis in production cultures and during in vitro biotransformations.

Polypodoaurein, a new phytoecdysone from Polypodium aureum L.

Abstract A new phytoecdysone was isolated from Polypodium aureum L. and its structure determined as 25- O -methylecdysterone.

Insecticidal activity of pyrrolizine derivatives isolated fromStreptomyces griseus

Mixtures of 5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one (1) and 5,6,7,7a-tetrahydro-3H-pyrrolizin-7a-ol-3-one (2) isolated from shaken cultures ofStreptomyces griseus exhibited contact killing effects on larvae ofLeptinotarsa decemlineata andAedes aegypti comparable with those of macrotetrolides and the commercial bioinsecticide Bactoculicid, respectively.Galleria mellonella (caterpillars),Anagasta kühniella andTetranychus urticae were insensitive to this action.

Effect of DL-ethionine on the biosynthesis of anthracyclines inStreptomyces coeruleorubidus

SummaryInhibitory action of DL-ethionine on 4-0-methylation and 10-COOH-esterification of the anthracyclinone ring inStreptomyces coeruleorubidus causes the formation of substances of the carminomycinone series, a concomitant drop in the production of daunomycinone derivatives and suppression of the biosynthesis of ε-rhodomycinone. The extent of inhibition depends on inhibitor concentration and the time of its addition to cultures. Ho formation of anthracyclinone ethyl-derivatives was found.

Characteristics ofStreptomyces globisporus strain 0234A forming endospores in submerged cultures

Thermosensitive submerged endospores formed byStreptomyces globisporus 0234 and its natural variant A resembled those of thermoresistant actinomycetes not only in their morphology and ultrastructure, but also in the content of dipicolinic acid. The production of endospores containing this substance is unusual inStreptomyces while other features of the strain indicate relatedness to other streptomycetes. Chemotaxonomic analysis of variant A revealed the cell wall to be of chemotype I and fatty acid content typical ofStreptomyces. Most characteristics of surface cultures of variant A coincided with those of the original strain 0234 and its endosporeless variant B. Both the strain 0234 and its variants A and B produced identical antibiotics and pesticidal compounds.

Immobilized preparations for the biotransformation of daunomycinone

SummaryBiotransformation of daunomycinone into 13-dihydrodaunomycinone was performed using immobilized cells, immobilized cell homogenate and immobilized enzymes, extract of the microorganism Streptomyces aureofaciens B-96. The whole cells and the homogenate were incorporated into a gelatine matrix by cross-linking with glutaraldehyde, while the enzyme extract was immobilized on modified bead cellulose. The highest level of conversion of daunomycinone into 13-dihydrodaunomycinone was achieved with the immobilized enzyme extract.

High-Performance Liquid Chromatography of New Semisynthetic Daunomycinone Derivatives

Abstract Reversed-phase HPLC utilizing LiChrosorb RP-8 was used to separate reaction mixtures of new semisynthetic daunomycinone derivatives and determine their relative occurrence. Chromatographic behaviour of the following compounds was studied: daunomycinone (I), 7(S) and 7(R)-0-(2-hydroxyethyl)-13-ethyleneacetal daunomycinone (II and III), 13-ethyleneacetal daunomycinone (IV), 13-ethyleneacetal bisanhydrodaunomycinone (V), 7(S) and 7(R)-0-(3-hydroxypropyl)-13-propyleneacetal daunomycinone (VI and VII), 13-propyleneacetal daunomycinone (VIII), 13-propyleneacetal bisanhydrodaunomycinone (IX), 7(S) and 7(R)-0-(4-hydroxybutyl) daunomycinone (X and XI), 4-toluenesulfonylhydrazone daunomycinone (XII).