Protein biosynthetic system incorporations

In order to use fluorinated amino acids to study biological systems, they need to be synthesized and incorporated. Despite the challenges in both steps, there are several methods available. For instance, enantiomerically pure fluorinated amino acids may be prepared by asymmetric synthesis or by stereochemical resolution using enzymatic methods [48], Fluorinated amino acids can be introduced into proteins biosynthetically, or chemically by SPPS. Several reviews that detail the synthesis of enantiomerically pure fluorinated amino acids and incorporation methods into proteins are available [48-51],... 

The incorporation of 3H from [3H]arabinose into Fer-Ara2 units showed a lag of about 4.2 min, after which it too became linear. This means that as little as 0.7 min after their incorporation into a (possibly still nascent) polysaccharide, [3H]arabinose residues were susceptible to feruloy-lation. The feruloylation reaction is thus likely to have been occurring in the endomembrane system, co-synthetically, as one of the highly regulated parts of the sophisticated polysaccharide-biosynthetic machinery. This can be compared to the co-translational modification known to occur in many proteins. 

Thus, the lipid biosynthetic enzyme system evolved in extreme halophiles to utilize the (halophilic) mevalonate pathway for synthesis of virtually all of its hydrocarbon (isoprenoid/isopranoid) chains, rather than the (non-halophilic) fatty-acid synthetase system which was retained only for synthesis of normal fatty acid chains required for incorporation into proteins of the red membrane (Pugh and Kates, unpublished data). Starting from acetate and involving lysine, which provides the branch-methyl and methine carbons [88]), the mevalonate pathway proceeds to geranylgeranyl-PP (GG-PP) [13,15,89] as follows ... 

The squalestatins, e.g. 6.28, also known as the zaragozic adds, have attracted considerable interest as inhibitors of squalene synthase and hence of cholesterol biosynthesis and lipid deposition in the circulatory system. They are also inhibitors of farnesyl protein transferase and thus they may have other potentially useful biological applications. They are formed by Phoma spedes and also by Setosphaeria khartoumensis. The squalestatins are characterized by a dioxabicyclo-octane core bearing three carboxyl groups and two polyketide chains, one of which is attached as an ester. The biosynthetic incorporation of succinic acid into part of the bicyclo-octane, together with its oxygenation pattern, indicate that it may be derived via oxaloacetic acid. Both the polyketide chains have several pendant methyl groups attached to them, which arise from methionine, whilst benzoic add ads as a starter unit for one of the chains. These complex structures are thus the summation of several biosynthetic pathways. 

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