Antibiotics biogenesis

By analogy with the biogenesis of oximes via oxidation of amino acids or biogenic amines, the biosynthetic pathway for insertion of the ketoxime function into the antibiotic, nocardicin A (18), was shown to be dependent on the oxidation of the corresponding primary amine precursor of 18 by cytochrome PTSO ". Similarly, the formation of the ketoxime bond of verongamine (17) is attributed to the oxidation of a primary amine precursor . 

Part of the biogenesis of cephalosporins was confirmed by isolating 13C-labeled compounds [1014]. Adding [2-13C]-acetate to cultures of Cephalosporium acremonium yielded an antibiotic labeled at C-l 1, -12, -13, -14 and -19 (marked with asterisks in the formula) [l-13C]-acetate, on the other hand, yielded a compound labeled at positions 10, 15 and 18 (symbolized by in the formula). 

Katz, E., and A. L. Demain, The peptide antibiotics of Bacillus Chemistry, biogenesis and possible functions. Bacte-riol. Rev. 41 449, 1977. A description of several peptide antibiotics showing the distribution of D-amino acid in these compounds. 

Cane DE, Celmer WD, Westley JW. Unified stereochemical model of polyedier antibiotic structure and biogenesis. J. Am. Chem. Soc. 

Thomas, R. Biogenesis of Antibiotic Substances. Vanek, Z. and Hestalek, Z., ed. p. 155. London - New York Academic Press 1965... 

A resurgence of interest and accomplishment in the field of biosynthe sis of natural products - including antibiotics - has occurred. The powerful methods for determination of a new structure with small amounts of material (mass and nmr spectroscopy, etc.) together with the development of 13C nmr spectroscopy for following the pattern of incorporation of precursors into these structures is one major reason. The subject of biogenesis of antibiotics has not been dealt with specifically in this series and this brief review will include some literature from earlier years than 1976. 

The biogenesis of monesin, a polyetrer ionophore antibiotic, proceeds from five acetate, seven propionate, and one butyrate molecules. A single methyl group from L-methionine is also present 38. Narasin, (10) another... 

A series of papers on the biogenesis of the FOMYCINS (25) has appeared 92>93>91t. These pyrazolopyrimidine antitumor antibiotics are made from lysine (two carbons), glutamate, and ribose. At least three nitrogens including those in the pyrazole ring are derived from lysine. 

R. Bentley, in Biogenesis of Antibiotic Substances ed. Z. Vanek and Z. Hostalik, Publishing house of the Czechoslovak Academy of Sciences, Prague, 1965, p. 241. 

Several reviews are available of the most important members of this group, the penicillins - and the cephalosporins, which from the point of view of biogenesis can be regarded as peptides. They are not, however, considered here, because they are not real polypeptide antibiotics. 

Polyether lonophores. Isolation and identification of antibiotic X-14885A was reported.Its structure is closely related to A-23187 and cezomycin, members of the pyrrolether class of natural ionophores. Aspects of the discovery and ionophoric properties of the X-14868 complex were described. Another new naturally derived agent, CP-53607 (32), was reported to be effective t ainst coccidia and as a rumen propionic acid stimulant. The C-26 urethane analogs of monensin transported both Rb and Ca. Their antibacterial and anticoccidial activities were also reported as greater than monensin. Microbial conversion of grisorixin by Streptomyces rimosus was found to produce an inactive and detoxified product. A unified stereochemical model of polyether antibiotic structure and biogenesis was proposed. Ibtal synthesis of ionophores continued to be of interest and the unnatural enantiomer of lasalocid A was found to have similar biolc cal properties to the natural product. ... 

G. G. F. Newton, and S. C. Warren In Z. Vanek and Z. Hostalek Biogenesis of Antibiotic Substances, S. 169. Prag Verlag der Tschechoslowaki-schen Akademie der Wissenschaften 1965. 

In Biogenesis Antibiotic Substances, Mater. Panel Discussion Congr. Antibiotic, Prag 1964, S. 155. 

Compounds with rearranged cadinane skeletons include the fungal antibiotic heptelidic acid (203), the most unusual endo-peroxide qinghaosu (204), which is an active principle from the Chinese medicinal herb Artemisia annua L., and koidzumiol (205). The biogenesis of the latter compound is considered to be as shown in Scheme 24. Some further derivatives of abrotanifolone (206) have also been isolated. ... 

The rifamycins are a family of closely related antibiotics of remarkable interest because of their structure, biogenesis, mechanism of action, and therapeutic efficacy. The rifamycins are the first natural compounds to be assigned a structure with an aromatic moiety spanned by an aliphatic bridge therefore they are ansa compounds. The first members of this class of agents were isolated from crude material extracted from fermentation broths of Nocardia mediterranei containing a complex mixture of several microbiologically active substances and were initially... 

Contents R. W. FRANCK, The Mitomycin Antibiotics — N. H. FISCHER, E J. OLIVIER, and H. D. FISCHER, The Biogenesis and Chemistry of Sesquiterpene Lactones — Author Index — Subject Index. 

If one mitochondrial population is favored over the other this would result either in a normal mitochondrial population after elimination of the defective type or in a cell with only defective mitochondria. This may result from different rates of biogenesis, from different degradation rates of mitochondria, or both. An intracellular mitochondrial selection process is known to occur during the induction of antibiotic-resistant mutants in yeast (Birky, 1973). Such amplification of a mutagenic defect may also develop in resting animal cells. 

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