Streptomyces fradiae, antibiotics from

Miao, V., Brost, R., Chappie, J. et al. (2006) The lipopeptide antibiotic A54145 biosynthetic gene cluster from Streptomyces fradiae. Journal of Industrial Microbiology Biotechnology, 33, 129. 

Antibiotic 34-1 (207) is the most recent of several known antibiotics (34-2 X-14881 E=8-0-methyl-3, 34-3 6-deoxy-8-0-methylrabelomycin 155, 34-4 8-0-methylrabelomycin 156). All are active against gram-positive bacteria and were isolated from Streptomyces fradiae strain 34, which is a construct obtained by intraspecific protoplast fusion of two S. fradiae strains. The parent strains were known as producers of the aminoglycoside antibiotic neomycin and the macrolide antibiotic tylosin, respectively [146]. Because of its reduced C-1 carbonyl, 207 resembles emycin A and hatomarubigin C (203), its closest relative. 

Compound V or glycidol phosphate was used by Rose and O Connell (1969) to study muscle triosephosphate isomerase because it closely resembles the presumed ene-diol intermediate in this enzyme s reaction mechanism. Coincidentally, it also proved to be an effective inhibitor of enolase even though it is not closely analogous to substrates of this enzyme. The structure of glycidol phosphate is similar to phosphononomycin (DC), an antibiotic isolated from fermentation broths of Streptomyces fradiae (Christensen et al. 1969). 

Tylosin 33 from Streptomyces fradiae is a representative member of the large family of 16-membered macrolide antibiotics commonly utilised in veterinary medicine. The aglycone core, tylactone 34 is constructed from two acetate, five propionate and one butyrate units [68, 69]. The processive mechanism for its biosynthesis was demonstrated by the pioneering contributions of Hutchinson... 

Some epoxides carry functional groups. The compound (lR,2S)-(-)-(l,2)-cpox-ypropyl phosphonic acid (fosfomycin) is a clinically important drug with wide-spectrum antibiotic activity. It was isolated originally from a fermentation broth of Streptomyces fradiae and prepared mainly by epoxidation of cfs-l-propenylpho-sphonic acid (CPPA) [42] followed by optical resolution of the racemic epoxide with chiral amines. Recently, chiral W (salen) and Mo (salen) complexes have been used in the asymmetric epoxidation of CPPA [43]. 

Fosfomycin, the (IR,IS) (-)-l,2-cpoxy propylphosphonic acid, formerly called phosphonomycin, is a low-molecular-weight antibiotic of unusual structure that was originally isolated in 1969 from used culture medium of Streptomyces fradiae (Figure 4.l),i. 86-i88 yjjg structure was established by... 

This was not the end of the story, and over the years, several other antibiotics of the same structural type as streptomycin were discovered and subsequently entered clinical practice. These include neomycin (1949) from Streptomyces fradiae (especially for dermatological infections) kanamycin (1957) from Streptomyces kanamyceticus (initially used for infections caused by pseudomonads - organisms that are especially dangerous for bum victims - but has now been replaced by safer drugs) gentamicin (1963) from... 

Tilmicosin. The macrolide antibiotic tylosin is a fermentation product of Streptomyces fradiae. Tylosin is converted to desmycosin by acid hydrolysis to remove the mycarose ring and tilmicosin is produced from desmycosin by reductive amination of e C-20 aldehyde with 3,5-dimethylpiperidine (/). Tilmicosin is a mixture of diastereomers having the methyl groups of the piperidine ring approximately 85% cis and 15% trans. 

Tylosin [46-49] (Fig. 6), produced by Streptomyces fradiae, was one of the first antibiotics for which a comprehensive set of blocked mutants was isolated. They were used to help define the biosynthetic pathway. Whereas erythromycin is a 14-membered macrolide, tylosin has a 16-membered lactone structure. The gene for the final step of biosynthesis was cloned by reverse genetics from the protein sequence of the enzyme [46], and specific segments of surrounding DNA were found to complement other classes of blocked mutants. The formation of tylosin aglycon, protylonolide, is involved in five polyketide synthases. 

In addition, note that antibiotic preparations themselves are often contaminated with DNA encoding antibiotic-resistant genes. Fluorescence spectroscopy and PCR amplification have shown that a number of antibiotic preparations are contaminated with significant amounts of DNA from the antibiotic-producing bacterium (for example, the gene ermSF of Streptomyces fradiae, which is responsible for resistance to MLS antibiotics) [115]. 

As well as clinical isolates, erm genes have been isolated from soil bacteria including antibiotic-producing microbes such as Bacillus licheniformis ermD [erm(D)]), B. sphaericus (ermG [erm(G) ), B. subtilis ermlM [erm C)]), B. anthracis (ermJ [erm(D)]), and B. licheniformis (ermK [erm(D)]) as well as Sac-charopolyspora erythreus (ermE erythromycin producer [erm E)]), Arthrobacter luteus (ermR or ermA, AR erythromycin producer [erm(R)]), and Streptomyces fradiae (ermSF [erm(S)]). 

A mass-spectrometric investigation of the antibiotics Paromomycin and Paromomycin II as their per(trimethylsilyl) derivatives has been made. A molecular ion was found in these tetrasaccharides containing amino sugars. The A-series of fragments was found to establish the sequence of the monosaccharide residues in the oligosaccharide. Essentially the same technique was used in a study of antibiotics from Streptomyces fradiae these were found to be tetrasaccharides containing an amino-deoxycyditol residue. " ... 

International free name for an aminoglycoside antibiotic isolated from cultures of Streptomyces fradiae. The substance, first isolated by Waksman in 1949 is made up of three components N. A, B (major components), and C. N. A is a degradation product of the two stereoisomers N. B and N. C. 

Mutant strains of macrolide-producing microorganisms, in which different steps of macrolide biosynthesis have been blocked, have yielded a wide variety of new compounds representing biosynthetic intermediates and shunt metabolites. This approach has been employed especially with Streptomyces fradiae, producer of the commercially important veterinary antibiotic tylosin three groups have independently isolated and identified many fermentation products which differ from tylosin in the number or type of saccharides and/or degree of... 

Further examples of BVMO reactions are reported in the biosynthesis of urdamycin (the antitumor antibiotic produced by the soil bacteria Streptomyces fradiae TU 2717) [38], jadomycin (a glycoside antibiotic produced by the soil bacterium Streptomyces venezuelae ISP5230) [39], and 5-alkenyl-3,3(2//)-furanones (isolated from Streptomyces aculeolatus NRRL 18422 and Streptomyces sp. Eco86) [40],... 

Fosfomycin is one of a few natural products containing a carbon-phosphorus (C— P) bond isolated from Streptomyces fradiae, Streptomyces viridochromogenes, and Streptomyces wedmorensis [73]. It was also isolated from Pseudomonas syringae and Pseudomonas viridiflava [74, 75], Fosfomycin is a highly effective antibiotic of low toxicity clinically utilized for the treatment of lower urinary tract infections [76] as well as methicillin-resistant [77] and vancomycin-resistant [78] strains of S. aureus. Moreover, fosfomycin is effective for the treatment of cephalosporin- and penicillin-resistant Streptococcus pneumonia [79] and ciprofloxacin-resistant E. coli [80], The antimicrobial activity of fosfomycin has been ascribed to the inactivation of UDP-GlcAAc-3-O-enolpyruvyltransferase (MurA), an essential enzyme that catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the cell wall, by covalent alkylation of an active site cysteine [81]. 

C23H46N6O14 630.648 Aminoglycoside antibiotic. Isol. from Streptomyces fradiae 3535. Active against gram-positive bacteria, fungi and yeasts Sol. H2O. Md +44.6 (c, 0.01 in H2O). 

Aminoglycoside antibiotic. Isol. from Streptomyces fradiae and Streptomyces kanamyceticus. Needles. 

Aminoglycoside antibiotic. Isol. from Streptomyces fradiae. Degradn. prod, of Neomycin B, N-23 and Neomycin C, N-24. Shows relatively weak activity primarily against gram-positive organisms. Cryst. (H2O or EtOH aq.). Mp 225-226° dec. [a] = +112.8 (c, 1.0 in H2O). Component of Neomycin, BAN, INN. 

Nucleoside-type antibiotic complex. Should not be confused with the antibiotic from S. fradiae and now called Neomycin A (see Neomycin A, N-22). Struct, revised in 1982. Isol. from Streptomyces sp. Shows broad spectrum of activity, but acutely toxic. 

Neomycin was first obtained by Waksman and Lechevalier from the culture fluid of Streptomyces fradiae. Later, it was shown to consist of closely related antibiotics, neomycins B and C. Both substances consist of three Ce units and one C5 unit linked glycosidically and neomycin B can be assigned the tentative structure LV. A fragment composed of a diamino-hexose and 2-deoxystreptamine, known as neamine, is common to neomycins B and C. The difference between the two substances resides in a second fragment, known as neobiosamine B or C, which consists of D-ribose linked to a diaminohexose. The latterwhich is different in the two neomycins, is known as neosamine B or C. 

An elegant alternative for a dynamic kinetic resolution of dimethyl(l-chloro-2-oxopropyl)phosphonate was reported by Feske and coworkers as a key step for the synthesis of (—)-fosfomydn (33) [62]. (lR,2S)-l,2-Epoxypropylphosphonic acid (fosfomycin. Scheme 4.14) was originally isolated from Streptomyces fradiae and is used as an antibiotic for the treatment of a variety of infections such as urinary tract or lung infections. In this work, a Ubrary of baker s yeast reductases was employed to reduce dimethyl(l-chloro-2-oxopropyl)phosphonate to the corresponding alcohol. Two reductases, YBR149wand YDR368w, showed good diastereoselectivities toward... 

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