One-carbon unit elongation

One research direction is the biocatalytic elongation of a one-carbon unit, still limited to very few catalysts. Equally, only very few examples of biocatalyzed ring closures are available and therefore are the subject of recent papers. 

The first step is carboxylation of acetyl CoA to malonyl CoA. This reaction is catalyzed by acetyl-CoA carboxylase [5], which is the key enzyme in fatty acid biosynthesis. Synthesis into fatty acids is carried out by fatty acid synthase [6]. This multifunctional enzyme (see p. 168) starts with one molecule of ace-tyl-CoA and elongates it by adding malonyl groups in seven reaction cycles until palmi-tate is reached. One CO2 molecule is released in each reaction cycle. The fatty acid therefore grows by two carbon units each time. NADPH+H is used as the reducing agent and is derived either from the pentose phosphate pathway (see p. 152) or from isocitrate dehydrogenase and malic enzyme reactions. 

In the synthesis of fatty acids the acetyl irnits are condensed and then are reduced to form straight hydrocarbon chains. In the oxo-acid chain elongation mechanism, the acetyl unit is introduced but is later decarboxylated. Tlius, the chain is increased in length by one carbon atom at a time. These two mechanisms account for a great deal of the biosynthesis by chain extension. However, there are other variations. For example, glycine (a carboxylated methylamine), under the influence of pyridoxal phosphate and with accompanying decarboxylation, condenses with succinyl-CoA (Eq. 14-32) to extend the carbon chain and at the same time to introduce an amino group. Likewise, serine (a carboxylated ethanolamine) condenses with... 

Polyketides are made by the sequential activity of domains of large, multifunctional enzymes called polyketide synthases (PKSs) (Fig. 6a and b). Polyketides are formed by the condensation and modification of acyl units derived from acyl-CoA precursors. Domains are organized in modules and each module carries out the series of steps necessary for one cycle of polyketide chain elongation. A single protein can have more than one module, and several different proteins together can make up a PKS. The number of modules determines the size of the polyketide. A growing polyketide chain is tethered to the enzyme as a thiol ester and moves sequentially from the N- to the C-terminus of a module, lengthened by two carbon units per module. The first module in a PKS... 

Some insects use hydrocarbons as sex pheromones. For example, the housefly, Musca domestica, uses a mixture including (Z) -9-tricosene, the corresponding epoxide and ketone, and several methyl alkanes (2iI). The tricosene is derived by chain elongation of oleic acid, and the epoxide and ketone are made from it. The methyl alkanes are made de novo from acetate and propionate, with one propionate unit per molecule supplying the branch carbon. Propionate can arise from the degradation of valine or isoleucine, but not from succinate, although succinate may serve as an acetate precursor. 

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