Protein biosynthetic system

Furukawa, K., Mizushima, N., Noda, T., and Ohsumi, Y. A protein conjugation system in yeast with homology to biosynthetic enzyme reaction of prokaryotes, J Biol Chem 2000, 275, 7462-7465. 

R Dieckmann, H von Dohren. Structural model of acyl carrier domains in integrated biosynthetic systems forming peptides, polyketides and fatty acids based on analogy to the E. coli acyl carrier protein. In RH Baltz, GD Hegeman, PL Skatrud, eds. Developments in Industrial Microbiology. Fairfax, VA Society for Industrial Microbiology, 1997, pp 79-87. 

It is clear from this discussion that carnitine is required in humans for the oxidation of long-chain fatty acids. In humans, carnitine is derived from both dietary sources and endogenous biosynthesis. Meat products, particularly red meats, and dairy products are important dietary sources of carnitine. Since biosynthesis can meet all physiological requirements, carnitine is not an essential nutrient. Premature infants are an exception to this rule as they lack a mature biosynthetic system and have limited tissue carnitine stores. As many infant formulas, particularly those based on soy protein, are low in carnitine, premature infants receiving a significant part of their nutrition from such formulas may be susceptible to carnitine deficiency. 

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],... 

In contrast to the biosynthetic systems for catecholamines and serotonin discussed earlier, there appear to be no posttranslational modifications such as protein phosphorylation or proteolytic activation that regulate the catalytic state of choline acetyltransferase. A more detailed discussion of acetylcholine synthesis may be found in Blusztajn and Wurtman (1983). 

Figure 1 Hypothetical pentaketide biosynthetic system, which illustrates the enzymatic logic of type I modular polyketide synthases (PKSs) and the catalytic role of acyl transferase (AT) domains. Each AT domain selects substrates from the cellular pool and tethers them as thioesters to acyl carrier protein (ACP) domains. In a typical PKS module, the AT and ACP domains are present in all modules. The ketosynthase (KS) domain is present in all chain extension modules. The dehydratase (DH), enoyl reductase (ER), and ketoreductase (KR) domains are optional domains. The final thioesterase (TE) domain catalyzes the release of the product from the PKS.

Typically, the last domain in the final module of modular PKS and NRPS systems is a thioesterase (TE) domain. This domain catalyzes the release of the assembled polyketide or peptide chain from carrier protein domain within the last module of the PKS or NRPS. Separately encoded, stand-alone TE enzymes are also found in some systems, such as the coelichelin biosynthetic system. TE domains catalyze two related types of chain release reactions. The first type is the hydrolysis or intermolecular condensation with a soluble amine and the second is intramolecular amide or ester bond formation. These chain release reactions result in distinct metabolic products. The intermolecular reactions lead to linear products with a carboxyl-terminus, whereas the intramolecular reactions lead to cyclic products. Sequence comparisons of TE domains from various modular PKSs that assemble known metabolic products have established a correlation between the phylogenetic relatedness of the domains and the type of chain release reaction catalyzed. " However, this predictive tool, which has been developed by Ecopia BioSciences, is not yet publicly accessible. 

The ribosomal protein biosynthetic machinery encompasses all three types of modnlarity. The ribosome catalyst can be separated from the element determining the snbstrate specificity, i.e. the mRNA template. The two acylated tRNA snbstrates for the peptide-bond formation bind to different ribosomal sites, the A and P sites, and the mnltistep pathway catalyzed by the modnlar system may be reprogrammed by codon choice. 

The o anization of peptide biosynthetic systems is primarily approached from the amino acid composition of the product. From the protein side, large multifunctional enzymes... 

The basic principle of polyketide assembly is highly related to that of fatty acid biosynthesis [14, 16]. In both biosynthetic systems, an acyl-primed ketosynthase (KS) catalyzes chain extension by decarboxylative Claisen condensation with malonate activated by its attachment to coenzyme A or an acyl carrier protein (ACP) via a thioester bond (Scheme 2.2). hi fatty acid synthases (FASs), the resulting ketone is rednced to the corresponding alcohol by a ketore-ductase (KR), dehydrated by action of a dehydratase (DH) to give the alkene with snbseqnent donble-bond reduction by an enoyl rednctase (ER) yielding the saturated system (cf. Section 3.2). The latter can then be transferred onto the KS domain and enter the next cycle of chain extension and complete rednction. This homologation process facilitates the assembly of long-chain satnrated fatty acids, for example, palmitic acid, after seven cycles, which will ultimately be released from the catalytic system by saponification of the... 

These studies indicate that the major outer membrane proteins (and possibly some cytoplasmic membrane proteins) are produced in a somewhat different manner than the cytoplasmic proteins. Furthermore, it appears that individual outer membrane proteins have their own specific biosynthetic systems. It has been suggested that such specific systems for the outer membrane protein biosynthesis may be achieved by one mechanism or a combination of the following mechanisms (a) differentiation of ribosomes, (b) compartmentalization of ribosomes, and (c) differentiation of factors required for protein synthesis. ... 

Bacteria are vulnerable to the selective attack of chemotherapeutic agents because of the many metabolic and molecular differences between them and animal cells. The biology of vims replication, with its considerable dependence on host-cell energy-producing, protein-synthesizing and biosynthetic enzyme systems, severely limits the opportunities for selective attack. Another problem is that many vims diseases only become apparent after extensive viral multiplication and tissue damage has been done. 

As we have noted, the outcome of a virus infection is the synthesis of viral nucleic acid and viral protein coats. In effect, the virus takes over the biosynthetic machinery of the host and uses it for its own synthesis. A few enzymes needed for virus replication may be present in the virus particle and may be introduced into the cell during the infection process, but the host supplies everything else energy-generating system, ribosomes, amino-acid activating enzymes, transfer RNA (with a few exceptions), and all soluble factors. The virus genome codes for all new proteins. Such proteins would include the coat protein subunits (of which there are generally more than one kind) plus any new virus-specific enzymes. 

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