Biosynthesis of Polymers

Polymers produced by biological routes invariably are made by some kind of stepwise polymerization rather than a chain polymerization. An interesting example is afforded by di -l,4-polyisoprene. Isoprene can be made from propylene through a sequence of dimerization, isomerization, and steam demethanization [59]  

FIGURE 4.21 Intermediates in the biosynthesis of rubber. (Data from Archer, B. L. et al. chap. 3 in L. Bateman, ed., The Chemistry and Physics of Rubber-Like Substances. 1963. New York. Copyright Wiley-VCH Verlag GmbH Co. KGaA. Reproduced with permission.) 

FIGURE 4.22 (a) Cellulose repeating structure, P-o-glucopyranose unit (b) D-glucose. 

A close approximation to test tube creation of a biologically active substance was made at Stanford University [59], Using a tritium-labeled (-F) DNA as a template, workers were able to make an artificial (-) DNA from modified monomer units. The resulting (-) DNA was different from that usually found in nature, but it was able to act as a reverse template to reproduce (-F) DNA identical with the starting material. This experiment does not demonstrate the total synthesis of living matter from the elements. It does show that genetic modification by chanical means is a distinct possibility. Total syntheses of enzymes have been reported (see Section 15.3). 

FIGURE 4.24 Engineering new polymers via bacterial cell growth. 

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Developments in genetic engineering have raised the possibility of producing poly(hydroxyalkanoate) polymers in plants. The plant Arabidopsis thaliana has accepted genes from the bacterial species Alcaligenes eutrophus, which has resulted in plant leaves containing as much as 14% poly(hydroxybutyric acid) on a dry mass basis. Transgenic Arabidopsis thaliana and Brassica napus (canola) have shown production of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate. If yields can be raised to acceptable levels, plant-synthesized poly(hydroxyalkanoate) materials would represent a tremendous advance in the biosynthesis of polymers because of the ability of photosynthesis to provide the raw materials used to make the polymers. 

III. BIOSYNTHESIS OF POLYMERS, GLYCOPROTEINS, MUCINS, AND GLYCOLIPIDS CONTAINING SIALIC ACID... 

All these polyesters are produced by bacteria in some stressed conditions in which they are deprived of some essential component for thek normal metabohc processes. Under normal conditions of balanced growth the bacteria utilizes any substrate for energy and growth, whereas under stressed conditions bacteria utilize any suitable substrate to produce polyesters as reserve material. When the bacteria can no longer subsist on the organic substrate as a result of depletion, they consume the reserve for energy and food for survival or upon removal of the stress, the reserve is consumed and normal activities resumed. This cycle is utilized to produce the polymers which are harvested at maximum cell yield. This process has been treated in more detail in a paper (71) on the mechanism of biosynthesis of poly(hydroxyaIkanoate)s. 

Much of protein engineering concerns attempts to explore the relationship between protein stmcture and function. Proteins are polymers of amino acids (qv), which have general stmcture +H3N—CHR—COO , where R, the amino acid side chain, determines the unique identity and hence the stmcture and reactivity of the amino acid (Fig. 1, Table 1). Formation of a polypeptide or protein from the constituent amino acids involves the condensation of the amino-nitrogen of one residue to the carboxylate-carbon of another residue to form an amide, also called peptide, bond and water. The linear order in which amino acids are linked in the protein is called the primary stmcture of the protein or, more commonly, the amino acid sequence. Only 20 amino acid stmctures are used commonly in the cellular biosynthesis of proteins (qv). 

In one of the early experiments designed to elucidate the genetic code, Marshall Nirenberg of the U.S. National Institutes of Health (Nobel Prize in physiology or medicine, 1968) prepared a synthetic mRNA in which all the bases were uracil. He added this poly(U) to a cell-free system containing all the necessary materials for protein biosynthesis. A polymer of a single amino acid was obtained. What amino acid was polymerized ... 

Figure 48-9. Structure of heparin. The polymer section illustrates structural features typical of heparin however, the sequence of variously substituted repeating disaccharide units has been arbitrarily selected. In addition, non-O-sulfated or 3-0-sulfated glucosamine residues may also occur. (Modified, redrawn, and reproduced, with permission, from Lindahl U et al Structure and biosynthesis of heparin-like polysaccharides. Fed Proc 1977 36 19.)...

It is important to note that the foregoing, biosynthetic-polymer modification is usually incomplete. In fact, only a fraction of the heparin precursor undergoes all of the transformations shown in Scheme 1. However, as the product of each enzymic reaction constitutes the specific substrate for the succeeding enzyme, the biosynthesis of heparin is not a random process. Thus, sulfation occurs preferentially in those regions of the chain where the amino sugar residues have been N-deacetylated and N-sulfated, and where D-glucuronic has been epimerized to L-iduronic acid.20... 

Fig. 7. Biosynthesis of cutin monomers, and the polymer from the monomers (inset, bottom left). ACP = acyl carrier protein...

Martin DP, Zhang S, Su L, Lenz RW (1999) Extracellular polymerization of 3-hydroxyal-kanoate monomers by the synthase from Alcaligenes eutrophus. In Steinbuchel A (ed) Biochemical principles and mechanisms of biosynthesis and biodegradation of polymers. Wiley-VCH, Weinheim, pp 168-175... 

MATSUDA, S.P.T., On the diversity of oxidosqualene cyclases. In Biochemical Principles and Mechanisms of Biosynthesis and Degradation of Polymers (A. Steinbuchel, ed,), Wiley-VCH, Weinheim. 1998, pp. 300-307. 

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