Bacteria Streptomyces

The natural products Mycoticin A (22, R = H) and B (22, R = Me) belong to the skipped-polyol-polyene class of antibiotics. Our analytical interest here is to use this very complex molecular structure to demonstrate some of the tools employed, mainly for the elucidation of the polyene part of the molecule. This family of polyene macrolide class was discovered in 195045 with the finding of Nystatin (23), which is produced by the Streptomyces bacteria. The exact structure was elucidated only in 1970 by Chong and Rickards46 and, in 1971, Nystatin Ai (23) and A2 (not shown in this review) were separated. 

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. 

Pravastatin, a 3-hydroxy-3-methyl glutaryl CoA reductase inhibitor applied as a therapeutic agent for hypercholesterolemia, can be synthesized by stereo- and regioselective hydroxylation of compactin by the soil microorganism Streptomyces sp. Y-110 (Fig. 22) [152]. The fermentative production of pravastatin has already been applied on an industrial scale by Sankyo Co. using different Streptomyces bacteria strains [153, 154]. 

Streptomyces bacteria are familiar to us as important sources of antibiotics used in medicine. Avermectins, including abamcctins and ivermectins, are naturally occurring antibiotics that have insecticidal properties that are useful in the garden as well as on pets and livestock. 

The genomes of Streptomyces bacteria are very large by bacterial standards. Pulsed-field gel electrophoresis studies have revealed that the genomes of... 

Recently, a large number of Streptomyces bacteria with antifungal activity isolated from samples collected in the Trondheim fjord in Norway were found to produce polyene compounds. Investigation of the polyene-containing extracts revealed that most of the isolates produced the same compound candicidin D. Analysis of... 

Another member of the family is daunomycin. Both of these antibiotics are produced in strains of Streptomyces bacteria by a pathway called polyketide biosynthesis. 

The molecule was isolated in 2006 from a strain of Streptomyces bacteria and shown to be active against drug-resistant bacterial strains (see Real Life 20-2). It inhibits the growth of cell membranes in the pathogen by a new mechanism that does not occur in humans, and it is therefore essentially nontoxic. A holdup for advancement to clinical trials is its fast clearance from the body, and current intensive work is devoted to modifying the drug s skeleton to improve its physiological half-life. 

Some bacteria are resistant to penicillin, because they produce an enzyme, penicillinase, that destroys the /3-lactam ring in the antibiotic. Synthesis of analogs afforded a partial solution to this problem. Ultimately, however, it became necessary to turn to antibiotics with completely different modes of action. Erythromycin, produced by a strain of Streptomyces bacteria first found in soil samples in the Philippines in 1952, functions in a distinct manner. It is a large ring lactone that interferes with the bacterial ribosome, its cell-wall protein S5mthesis factory. Although erythromycin is unaffected by penicillinase, bacteria resistant to it have developed over the decades since its introduction into the antibiotic arsenal. 

In 2009, Snyder s group reported the first asymmetric total synthesis of ( )-napyradiomycin A1 93, a nonsteroidal estrogen antagonist isolated from Streptomyces bacteria... 

Carbamate hydrolysis is frequendy observed as the initial reaction for pesticides having carbamate bonds, such as aldicarb, carbofuran, carbaryl, and benomyl (eq. 12) (19). Numerous genera of carbamate-hydroly2ing bacteria have been identified, including Pseudomonas, Jhihrobacter, Bacillus, Nocardia, Achromobacter, Flavobacterium, Streptomyces, Alcaligenes, A spirillum, Micrococcus, and Bhodococcus. 

Three more antibiotics, all discovered about 1953, are also derivatives of cytosine. Amicetin, bamicetin and plicacetin may all be isolated from Streptomyces plicatus and all have some activity against some acid-fast and Gram-positive bacteria as well as some other microbial systems (69MI21301). Structural work in this area is fascinating (62JOC2991). 

Erythromycin Streptomyces erythreus Gram-positive bacteria Protein synthesis... 

Natamycin is a fungicide used to keep cheese from getting moldy. It works by making holes in the cell membranes of fungi, so their insides leak out. It is produced by Streptomyces natalensis bacteria. 

However, important as the /3-lactams are, they are but one of mai r families of anhbiotics (Chapter 5). Furthermore, most industrial microorganisms used to make j8-lactams are fungi this is atypical of anhbiotics as a whole where bacteria, particularly Streptomyces spp., predominate. Chapter 5 and some of the further reading at the end of this chapter provide the broad perspechve, including informahon on those anribiohcs made by total or partial chemical synthesis, against which this present account with its necessarily selechve subject matter should be read. 

The oxidation of cholesterol to cholest-4-ene-3-one is carried ont by an oxidase in several bacteria. This activity has been fonnd in Brevibacterium sterolicum and Streptomyces sp. strain SA-COO (Ohta et al. 1991), and the extracellnlar enzyme that has been purified from Pseudomonas sp. strain ST-200 (Donkyn and Aono 1998) has a preference for 3p-hydroxy componnds. 

Some metals can be converted to a less toxic form through enzyme detoxification. The most well-described example of this mechanism is the mercury resistance system, which occurs in S. aureus,43 Bacillus sp.,44 E. coli,45 Streptomyces lividans,46 and Thiobacillus ferrooxidans 47 The mer operon in these bacteria includes two different metal resistance mechanisms.48 MerA employs an enzyme detoxification approach as it encodes a mercury reductase, which converts the divalent mercury cation into elemental mercury 49 Elemental mercury is more stable and less toxic than the divalent cation. Other genes in the operon encode membrane proteins that are involved in the active transport of elemental mercury out of the cell.50 52... 

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