Polymers isoprenoids

The antimicrobial action of ethambutol, like that of isoniazid, is specific for mycobacteria, suggesting a target in the unique components of the mycobacterial cell wall. Cells treated with ethambutol accumulate an isoprenoid intermediate, decaprenyl-arabinose which is the source ofarabinose in the arabinogalactan polymer. This suggests that ethambutol blocks assembly of the arabinogalactan through inhibition of an arabinosyl transferase enzyme. 

Formally, isoprenoids are derived from a single common building block, isoprene (2-methyl-l,3-butadiene), a methyl-branched compound with five C atoms. Activated isoprene, isopentenyl diphosphate, is used by plants and animals to biosynthesize linear and cyclic oligomers and polymers. For the isoprenoids listed here—which only represent a small selection—the number of isoprene units (1) is shown. 

This process has, however, not yet found industrial application. Similarly, poly-isoprenoids can be epoxidized regioselectively in co-position to functional groups (Table 4, No. 16-19) Polymer-bound mediators can also be used in this... 

Continuation of the head-to-tail addition of five-carbon units to geranyl (or neryl) pyrophosphate can proceed in the same way to farnesyl pyrophosphate and so to gutta-percha (or natural rubber). At some stage, a new process must be involved because, although many isoprenoid compounds are head-to-tail type polymers of isoprene, others, such as squalene, lycopene, and /3- and y-carotene (Table 30-1), are formed differently. Squalene, for example, has a structure formed from head-to-head reductive coupling of two farnesyl pyrophosphates ... 

This proposal supported, with an earlier prediction of Sir Robert Robinson, that cholesterol was a cyclization product of squalene, a 30-carbon polymer of isoprene units. In 1953, Robert Bums Woodward and Bloch postulated a cyclization scheme for squalene (fig. 20.2) that was later shown to be correct. In 1956, the unknown isoprenoid precursor was identified as mevalonic acid by Karl Folkers and others at Merck, Sharpe, and Dohme Laboratories. The discovery of mevalonate provided the missing link in the basic outline of cholesterol biosynthesis. Since that time, the sequence and the stereochemical course for the biosynthesis of cholesterol have been defined in detail. 

The terpenoids form a large and structurally diverse family of natural products derived from C5 isoprene units (Figure 5.1) joined in a head-to-tail fashion. Typical structures contain carbon skeletons represented by (Cs) , and are classified as hemiterpenes (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C2o), sesterterpenes (C25), triterpenes (C30) and tetraterpenes (C40) (Figure 5.2). Higher polymers are encountered in materials such as rubber. Isoprene itself (Figure 5.1) had been characterized as a decomposition product from various natural cyclic hydrocarbons, and was suggested as the fundamental building block for these compounds, also referred to as isoprenoids . Isoprene is produced naturally but is not involved in the formation of... 

In addition to vitamin E, the isoprenoids and their derivatives up to cholesterol give rise to all the fat-soluble vitamins (A,D,E,K) and to coenzyme Q (used in electron transport in the Ferris Wheel Generator). Dolichol is an isoprene polymer that participates in the transfer of oligosaccharides during glycoprotein synthesis. 

Tobacco leaf has a complicated chemical composition including a variety of polymers and small molecules. The small molecules from tobacco belong to numerous classes of compounds such as hydrocarbons, terpenes, alcohols, phenols, acids, aldehydes, ketones, quinones, esters, nitriles, sulfur compounds, carbohydrates, amino acids, alkaloids, sterols, isoprenoids [48], Amadori compounds, etc. Some of these compounds were studied by pyrolysis techniques. One example of pyrolytic study is that of cuticular wax of tobacco leaf (green and aged), which was studied by Py-GC/MS [49]. By pyrolysis, some portion of cuticular wax may remain undecomposed. The undecomposed waxes consist of eicosyl tetradecanoate, docosyl octadecanoate, etc. The molecules detected in the wax pyrolysates include hydrocarbons (Cz to C34 with a maximum of occurrence of iso-Czi, normal C31 and anti-iso-C32), alcohols (docosanol, eicosanol), acids (hexadecanoic, hexadecenoic, octadecanoic, etc ). The cuticular wax also contains terpenoids such as a- and p-8,13-duvatriene-1,3-diols. By pyrolysis, some of these compounds are not decomposed and others generate closely related products such as seco-cembranoids (5-isopropyl-8,12-dimethyl-3E,8E,12E,14-pentadecatrien-2-one, 3,7,13-trimethyl-10-isopropyl-2,6,11,13-tetradecatrien-1al) and manols. By pyrolysis, c/s-abienol, (12-Z)- -12,14-dien-8a-ol, generates mainly frans-neo-abienol. 

Ethambutol is thought to block assembly of the arabinogalactan polysaccharide by inhibition of an arabinotransferase enzyme. Cells treated with ethambutol accumulate the isoprenoid intermediate decaprenylarabinose, which supplies arabinose units for assembly in the arabinogalactan polymer. 

Most microbially produced polymers are known to be stiff and not very flexible. However, one potential microbially derived polymer that is more supple is a lactic acid-P-methyl-5-valerolactone( M5VL)-lactic acid triblock copolymer. This was demonstrated by the overproduction of mevalonate in E. coli via enzymes from L. casei which generate mevalonate, a precursor of the isoprenoid pathway, from acetyl-CoA. Mevalonate is produced at over 80gl from glucose, dehydrated, and then reduced to form M WL. PLA-PPM5VL-PLA triblock copolymers were created to demonstrate physical properties such as elasticity and toughness [141]. 

For linear isoprenoid biosynthesis, elongation of the polymer chain can be described in two main phases as shown in Figure 9.5.3 ... 

Two mechanisms have been proposed for resin curing of butyl rubber. One proposal involves an ortho-methylene-quinone intermediate that abstracts an allyl hydrogen from the isoprenoid group of the butyl polymer chain and would occur via the formation of a six-membered ring ene intermediate. This would be followed by formation of a second ortho-methylene-quinone intermediate with another isoprenoid group of an adjacent butyl polymer chain to form a monophenol crosslink (Scheme 4.3). 

It has been well established that the enzymes required for the biosynthesis of the polymers of the outer membrane are localized in the inner membrane. Most importantly, the lipid-carrier molecules (poly-isoprenoid-phosphates) are found in this membrane. These molecules transfer newly synthesized, activated precursor molecules from the hydrophilic cytoplasmic environment into the lipophilic environment of the membrane, where the assembly into polymeric structures takes place. This assembly process is used for lipopolysaccharides, peptidoglycans, and capsular polysaccharides. In a subsequent step, the membrane-carrier molecules transfer the assembled polymers from the inner to the outer membrane. ... 

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