Streptomyces, aminoglycosides from

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

These individual steps are susceptible to inhibition by antibiotics of different groups. The examples shown originate primarily from Streptomyces bacteria, some of the aminoglycosides also being derived from Micromonospora bacteria. 

A variety of bacterial genera have been shown to produce aminoglycoside-aminocyclitol antibiotics. These include Streptomyces, Micromonospora, Bacillus, and so on. Only those compounds emanating from Streptomyces are named -mycins (e.g., tobramycin) while others are -micins (gentamicin), -osins, -asins, or -acins. The biosynthetic pathways for the aminoglycosides and the control of their expression are not well-studied. Streptomycin is the exception. 

Of the eight aminoglycosides that are currently used, five are synthesized from different versions of Streptomyces streptomycin (isolated from Streptomyces griseus), neomycin (isolated from Streptomyces fradiae), paromomycin (isolated from S. rimosus), kanamycin (isolated from Streptomyces kanamyceticus), and tobramycin (isolated from... 

Spectinomycin Spectinomycin, 4a,7,9-trihydroxy-2-methyl-6,8-fcw-(methylamino)-per-hydroxypyrano-[2,3-b]benzodioxan-4-one (32.7.1), which is isolated from products of the actinomycete Streptomyces spectabilis, is an aminocyclitol, yet it is not an aminoglycoside antibiotic since it does not contain either an amino sugar region or a glycoside bond [316-324]. 

Aminoglycosides streptomycin (first isolated from Streptomyces griseus (Krainsky) Waksman et Henrici, Bact. isolated from unspecified manured field soil Schatz 1944 MI)... 

The aminoglycoside antibiotic, obtained from Streptomyces griseus is the first antitubercular drug. 

Kanamycin is an aminoglycoside antibiotic. It is obtained from Streptomyces kanamyceticus bacterium and is soluble in water. There are 16 chiral centers in this molecule and no cavity. It contains two pyranose rings, six hydroxyl groups, and three amine groups. This characteristic makes the molecule capable of enantiorecognition of different antipodes. 

Aminoglycoside antibiotics are produced in culture by strains of Streptomyces and Micromonsopora. Compounds obtained from Streptomyces have been given names ending in -mycin, whilst those from Micromonospora have names ending in -micin. 

The antibiotic lincomycin (Figure 8.32) from Streptomyces lincolnensis bears a superficial similarity to the aminoglycosides, but has a rather more complex origin. The sugar fragment is termed methyl a-thiolincosaminide, contains a thiomethyl group, and is known to be derived... 

Aminoglycosides are a group of bactericidal antibiotics originally obtained from various streptomyces species and sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. The group includes streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. 

Walker, J.B., 1995, Enzymatic synthesis of aminocyclitol moieties of aminoglycoside antibiotics from inositol by Streptomyces spp. Detection of glutamine-aminocyclitol aminotransferase and diaminocyclitol aminotransferase activities in a spectinomycin producer. J. Bacteriol. 177 818-822. 

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. 

Liou GF, Yoshizawa S, Courvalin P, GaUmand M. Aminoglycoside resistance by ArmA-mediated ribosomal 16S methylation in human bacterial pathogens. J. Mol. Biol. 2006 359(2) 358-364. Kawano Y, Kumagai T, Muta K, Matoba Y, Davies J, Sugiyama M. The 1.5 A crystal structure of a bleomycin resistance determinant from bleomycin-producing Streptomyces verticillus. J. Mol. Biol. 2000 295(4) 915-925. 

The clinical introduction of the penicillin group of antibiotics prompted an intensive search for novel antibiotic-producing organisms and Selman Waksman demonstrated the value of actinomycetes in this role, discovering the aminoglycoside streptomycin (81) from Streptomyces griseus in 1943 (126). Pharma-... 

Aminoglycosides. The names of those that are derived from streptomyces end in mycin, e.g. tobramycin. Others include gentamicin (from Micro-monospora purpurea which is not a fungus, hence the spelling as micin ) and semisynthetic drugs, e.g. amikacin. 

In the purposeful search that followed the demonstration of the clinical efficacy of penicillin, streptomycin was obtained from Streptomyces griseus in 1944, cultured from a heavily manured field, and also from a chicken s throat. Aminoglycosides resemble each other in their mode of action, and their pharmacokinetic, therapeutic and toxic properties. The main differences in usage reflect variation in their range of antibacterial activity crossresistance is variable. 

The anthracyclines are aminoglycosidic derivatives of tetracyclic compounds that contain an anthraquinone chromophore. Originally, dauno-mycin and adriamycin, its hydroxy analogue, were isolated from cultures of Streptomyces peucetiusd The main target of these drugs appears to be DNA, most likely by formation of an intercalation complex. The drugs also affect topoisomerase II, an enzyme which interacts with the DNA that has been modified by intercalation. ... 

The spectinomycins (O Fig. 20) have a fused three-ring system which consists of a 4,5-disub-stituted actinamine and an ulose. Spectinomycin is produced by Streptomyces spectabilis and Streptomyces flavopersius. It has been clinically used for treatment of the gonorrhea infection. A related structure has been discovered with spenolimycin which was isolated from the culture filtrate of Streptomyces gilvospiralis. Efforts have been directed toward semisynthetic aminoglycoside antibiotics to treat multi-drug resistant bacteria [94]. 

Trehalosamines are representative of the disaccharides in this class of aminoglycosides and are relatively weak antihiotics. Trehalosamine (compound 118) [117], its 2-epimer maimosylglucosaminide [118], and the 4-amino derivative compound 119 [119] were isolated from culture filtrate of Streptomyces and showed weak an-... 

Tetracyclines were the first broad-spectrum antibiotics and have been used successfully for decades to treat both gram-positive and gram negative bacterial infections (82). Chlortetra-cycline was the first tetracycline to be isolated, in 1948, from Streptomyces aureofaciens (83). Other common tetracyclines, such as oxytet-racycline and tetracycline, were isolated from Streptomyces sources in subsequent years. The abundance of natural, active tetracyclines, coupled with extensive synthetic alterations, provides a rich collection of compounds from which to build meaningful structure-activity relationships. As was found for the aminoglycosides, previous observations of tetracycline structure and activity can be rationalized from recent tetracycline/30S crystal structures (11,12). 

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