Structure desaturation

Sex pheromones in the Lepidoptera are multi-component mixtures consisting mostly of olefinic compounds possessing a terminal aldehyde, alcohol, or acetate moiety. Besides functional group differences, the constituents of lepidopteran sex pheromones vary in hydrocarbon chain length and in the specific number, location, and geometry of double bonds. These chemical structures are formed in biosynthetic pathways involving a limited number of enzymatic steps believed to use fatty-acyl thioesters of coenzyme A (acyl-CoA) as substrates. Key reactions are desaturation, limited [3-oxidation, and a small number of terminal functional group modifications (reviewed in Chapter 3). 

To date, the biosynthesis of the monoene and diene ketones found in some lymantrid pheromones, and which have been included in this chapter both because of their structural similarities to other Type II pheromones and because some lymantrid species produce mixtures of ketones and normal Type II pheromones, has not been studied. Such studies may be complicated by the instability of some of the diene ketones. One of the other significant unresolved questions in the biosynthesis of Type II pheromones is the desaturation that results in the production of l,3Z,6Z,9Z-tetraenes, for which the corresponding 3Z,6Z,9Z-trienes are not the precursors (Choi et al., 2007). 

The thiophene and the 3-substituted thiophenes 233 have been found to undergo ring dihydroxylation yielding the as fraar-dihydrodiol metabolites 234. Evidence is provided for a dehydrogenase-catalyzed desaturation of a heterocyclic dihydrodiol 234-< /234-rraas (R= Me) to yield the corresponding 2,3-dihydroxythiophene 235 as its preferred thiolac-tone tautomer 236. A simple model to allow prediction of the structure of metabolites, formed from Toluene dioxygenase (TDO)-catalyzed bacterial oxidation of thiophene substrates, has been presented (Scheme 17) <20030BC984>. 

The active site similarities listed above belie a remarkable functional diversity, which includes phosphate ester hydrolysis, dioxygen and NO reduction, reversible O2 binding, and O2 activation, the last of which includes enzymes involved in ribonucleotide reduction, hydrocarbon monooxygenation, and fatty acyl desaturation. At the overall protein level, the purple acid phosphatases (PAPs) seem to be completely unrelated, both structurally and functionally, to any of the others in this class. Similarly, the flavo-diiron enzymes form a structurally and probably functionally distinct family of proteins, catalyzing both dioxygen and NO reduction. These last two examples illustrate that attempts to shoehorn all of these enzymes into a single class can sometimes provide a simplistic and misleading view of their chemistry and biochemistry. 

Protoporphyrinogen oxidase converts protoporphyrinogen IX to the fully desaturated porphyrin in a reaction that uses O2 as the terminal electron acceptor (Fig. 3). The crystal structure of the homodimeric enzyme shows it has one FAD per monomer, which presumably mediates the porphyrin oxidation reaction (19). Like the decarboxylation mediated by coproporphyrinogen oxidase, this reaction also occurs in the mitochondrion. Mutations in the protoporphyrinogen oxidase gene are responsible for variegate porphyria (21). Acute attacks of this disease can be effectively treated by intravenous administration of hematin. 

The normal branched chain isovaleryl CoA (149) is then desaturated to the a,)3-enonyl CoA (150) by a flavin-linked branched chain acyl CoA dehydrogenase (equation 24). When the methylenecyclopropane acyl CoA (151) is exposed to acyl CoA dehydrogenase, time-dependent inactivation ensues with covalent modification of the bound FAD coenzyme (equation 25), possibly via a 6,5-adduct although the structure is unproven. ... 

The steps of prenylation and dehydrogenation which follow (94) in the biosynthesis of these neoechinulins is unknown but from knowledge of echinulin biosynthesis (Scheme 6) introduction of the side chain at C-2 may be the next step. Prenylation of the benzene unit seems, by inspection of structures (97) through (101), to depend on C-8—C-9 unsaturation rather than the structure of the dioxo-piperazine ring. The stereochemistry of the desaturation reaction has been explored with L-tryptophan (85) samples stereospecifically labelled with tritium at... 

A great diversity in molecular structure is observed among herbicides which inhibit carotene biosynthesis as is exemplified by the structures of norflurazon, fluridone and difunone (shown below). Nonetheless, many of these compounds, which comprise a subset of the larger group known as bleaching herbicides, appear to inhibit the same step in the biosynthetic pathway to the carotenoids (1 ). The inhibited step is the desaturation of 15-cis phytoene to 15- cis phytofluene (Figure 1) and the build-up of phytoene in plants and in cell-free systems which have been treated with these herbicides is well documented (2-4). 

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