Natural products, elimination, enzyme

The biosynthesis of many hydroxylated natural products proceeds through regio- and enantioselective modification of polyketides, which are assembled through chain elongation via acetate or propionate units [2]. The enzymes responsible for the chain elongation and subsequent reduction, elimination, aromatiza-tion, and further modifications are classified as polyketide synthases [3]. These multifunctional enzymes have been used for whole-cell biotransformation toward unnatural metabolites that are within the scope of combinatorial biosynthesis... 

The camptothecins are natural products that are derived from the Camptotheca acuminata tree, and they inhibit the activity of topoisomerase I, the key enzyme responsible for cutting and religating single DNA strands. Inhibition of the enzyme results in DNA damage. Topotecan is indicated in the treatment of patients with advanced ovarian cancer who have failed platinum-based chemotherapy and is also approved as second-line therapy of small cell lung cancer. The main route of elimination is renal excretion, and for this reason caution must be exercised in patients with abnormal renal function, with dosage reduction being required. 

Subsequent studies have shown (e.g. 5,6, Table I) that the liver of newborns is indeed deficient in enzymes needed not only for drug metabolism but also for the elimination of natural products. For example, because of the lack of UDP-glucuronyl transferase resulting in the inability to dispose of bilirubin, the newborn is at risk for brain damage by kernicterus. That PEP carboxykinase, the key catalyst of gluconeogenesis de novo is absent at 7 months and still at low titers 3 days after birth (Table I), probably contributes to the fact that transient hypoglycemia (which can also cause brain damage) represents a hazard to full term as well as premature infants. The immaturity of the hepatic enzyme composition imposes limitations on the choice of nutrients used to supplement or re-... 

C,oH oOg, Mu 226.19. P. is unstable in the free form and undergoes decarboxylation with elimination of water to give phenylpyruvic acid. It is an intermediate in the biosynthesis of many aromatic natural products by the shikimate pathway (see chorismic acid, shi-kimic acid). The biosynthesis of P. proceeds from chorismic acid by enzyme-catalyzed [3,3]sigmatropic rearrangement (Claisen rearrangement) under the action of chorismate mutase (EC 5.4.99.5). 

One of the most common types of elimination is the dehydration of an alcohol. Formally, these reactions are the microscopic reverse of the hydration of an alkene, and therefore we have already covered these reactions (see Section 10.2). However, several points should be stressed here, because dehydrations are commonly used in synthesis. Furthermore, dehydrations and hydrations are important biosynthetic reactions, as many natural products possess alkenes and alcohols. The Connections highlight at the end of this section discusses how enzymes catalyze these reactions. 

Meat products have to be stabilised in some cases, as meat lipids contain no natural antioxidants or only traces of tocopherols. Most muscle foods contain, however, an efficient multi-component antioxidant defence system based on enzymes, but the balance changes adversely on storage. The denaturation of muscle proteins is the main cause of the inbalance as iron may be released from its complexes, catalysing the lipid oxidation. Salting contributes to the negative effects of storage, as it enhances oxidation. Using encapsulated salt eliminates the deleterious effect of sodium chloride. 

Xylanolytic enzymes free of cellulases can be applied in the pulp and paper, textile, and food industries and in basic research. However, most microorganisms grown under natural conditions produce both xylanases and cellulases. Strategies to produce xylanolytic systems free of cellulases are elimination of cellulase activity by separation or inhibition, selection and construction of cellulase-negative strains, and finding conditions for separate production of xylanolytic systems by cellulolytic strains. 

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