Synthesis of unsaturated fatty acids

There is one very important feature of the type II system that should not be overlooked. Although a hard-wired type I mechanism may seem more efficient, it only produces a single product. In contrast, the type II system is not only responsible for producing all the diversity of fatty acids in membranes, the intermediates of the pathway are diverted for the synthesis of other key molecules. These include biotin, lipoic acid, and the quorum-sensing 

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A closely related E. coli protein is a 79-kDa multifunctional enzyme that catalyzes four different reactions of fatty acid oxidation (Chapter 17). The amino-terminal region contains the enoyl hydratase activity.32 A quite different enzyme catalyzes dehydration of thioesters of (3-hydroxyacids such as 3-hydroxydecanoyl-acyl carrier protein (see Eq. 21-2) to both form and isomerize enoyl-ACP derivatives during synthesis of unsaturated fatty acids by E. coli. Again, a glutamate side chain is the catalytic base but an imidazole group of histidine has also been implicated.33 This enzyme is inhibited irreversibly by the N-acetylcysteamine thioester of 3-decynoic acids (Eq. 13-8). This was one of the first enzyme-activated inhibitors to be studied.34... 

Both bacteria and plants have separate enzymes that catalyze the individual steps in the biosynthetic sequence (Fig. 17-12). The fatty acyl group grows while attached to the small acyl carrier protein (ACP).54 58 Control of the process is provided, in part, by the existence of isoenzyme forms. For example, in E. coli there are three different P-oxoacyl-ACP synthases. They carry out the transfer of any acyl primer from ACP to the enzyme, decarboxylate malonyl-ACP, and carry out the Claisen condensation (steps b, e, and/in Eq. 17-12)58a e One of the isoenzymes is specialized for the initial elongation of acetyl-ACP and also provides feedback regulation.58c The other two function specifically in synthesis of unsaturated fatty acids. 

The yeast growth is diauxic 17). Under the conditions of glucose repression, ethanol formation takes place even in the presence of oxygen. Yeasts require a small but finite oxygen supply for synthesis of unsaturated fatty acids, sterols, and nicotinic acid. These compounds which are essential to membrane functions are synthesized only aerobically 18). 

The formation of a yeast biofllm is largely associated with the presence of the nutrients required for the yeasts to grow. The major sources of carbon for this process are ethanol, glycerol and acetic acid, and those of nitrogen ammonium ion and amino acids (particularly L-proline). Oxygen is required for the synthesis of unsaturated fatty acids and sterols (Mauricio et al. 1991), and also for the assimilation of L-proline (Mauricio et al. 2001) (see Fig. 3B.4). 

In addition to chain elongation, fatty acids are modified by the introduction of double bonds (desaturation). Enz5maes, called desaturases, catalyze the synthesis of unsaturated fatty acids. They can use saturated or partially unsaturated fatty acids as substrates. A -Desaturase, for example, catalyzes the introduction of a double bond between carbons 9 and 10 of a fatty acid (covmting from the carboxylic acid end). Three examples of reactions of A-desaturases are shown in Figiue 9.95. 

Bloch, K. The biological synthesis of unsaturated fatty acids. Biochem Soc Symp, 24 (1963) 1-16. 

Grau, R. and de Mendoza, D. Regulation of the synthesis of unsaturated fatty acids by growth temperature in Bacillus subtilis. Mol Microbiol, 8 (1993) 535-542. 

Rosenfeld, I.S., D Agnolo, G., Vagelos, P.R. 1973. Synthesis of unsaturated fatty acids and the lesion in fabB mutants. J. Biol. Chem. 248 2452-2460. 

The synthesis of unsaturated fatty acids (Fig. 17.19) requires the participation of molecular oxygen and involves a mixed function oxidase (NADP-dependent) [72]. 

Modified fromRatledge C. 2004 Catala A, 2013 Condary Rand Yao JK, 2011. Figure 6. Synthesis of unsaturated fatty acids. 

The laboratory synthesis of unsaturated fatty acids has been pursued extensively. Whilst a few acids are easily isolated from appropriate natural sources (Section 4.9) it is necessary to resort to chemical synthesis when the acid occurs only in obscure sources or at low levels, or when an isotopically labelled sample is needed. Many synthetic procedures have been employed but those based on the reactivity of acetylene (ethyne) and its derivatives are the most common. The topic has been reviewed by Kunau (1973) and by Sprecher (1977, 1979). The Wittig reaction which is also useful in this connection and the synthesis of isotopically labelled compounds are covered in Sections 7.2 and 7.3 respectively. 

Isomerization of monoenes occurs in microorganisms for a number of reasons. One of these is because isomerization is an essential step in the synthesis of unsaturated fatty acids by anaerobes. A specific dehydrase (P-hydroxydecanoyl-ACP dehydrase) is capable of both dehydration of a 10-carbon intermediate in a growing fatty acyl chain as well as its isomerization from a trans-2 decanoyl-ACP to a af-d-decenoyl-ACP (32). The anaerobic pathway of unsaturated fatty acid synthesis accounts for 1-6% oleic acid in ruminal microorganisms (33). Other anaerobes, such as Streptococcus pneumoniae, isomerize a trans-2 decanoyl-ACP to a r-3-decenoyl-ACP during fatty acid synthesis without catalyzing the dehydration of P-hydroxy intermediates (34). 

Fig. 4. Fatty acid biosynthesis. Synthesis of unsaturated fatty acids by the anaerobic pathway in bacteria.

In order to define these desaturation systems further, we have carried out experiments using different radlolabelled precursors with both whole cells and cell-free extracts. In addition, we have utilised sterculate (a known inhibitor of A9 desaturation) to alter the synthesis of unsaturated fatty acids in R. gracilis. 

Bousquet, M.-P., Willemot, R.-M., Monsan, P. and Boures, E. (1999) Enzymatic synthesis of unsaturated fatty acid glucoside esters for dermo-cosmetic appheations. Biotechnol. Bioeng., 63, 730-736. 

Fig. 1. Pathways of synthesis of unsaturated fatty acids in protists, according to Kom et al. (1965). The unknown precursor was believed to occur in certain green algae in which 18 0 18 1(9) conversion had not been demonstrated.

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