Biosynthesis pathway

The net effect of the eight steps in the fattv-acid biosynthesis pathway is to take two 2-carbon acetyl groups and combine them into a 4-carbon butyryl group. Further condensation of the butyryl group with another malonyl AGP yields a 6-carbon unit, and still further repetitions of the pathway add two more carbon atoms to the chain each time until the 16-carbon palmitoyl ACP is reached. 

Now that we have provided you with an overview of the history of penicillin production, we will examine some more details of the biotransformation of -lactams. We will briefly outline the normal biosynthesis pathways that lead to their production and then consider how these products may be diversified in vitro to give a wider range of valuable compounds. We begin by briefly explaining how the fi-lactam antibiotics are effective as therapeutic agents. 

Scheme 9.38 Trichlorination of leucine with enzymes from the barbamide biosynthesis pathway (BarBl. BarB2 represent nonheme iron ketoglutarate-dependent halogenases).

During the second part of the experiment the examined compounds were applied repeatedly both to mice and rats. The same parameters, as after single administration were estimated in the serum and liver. Additionally, ALA-D and ALA-S, the two enzymes from haeme biosynthesis pathway were evaluated in the liver. 

The results obtained after 7-fold administration of all studied compounds, suggest that these compounds cause disturbances in the heame biosynthesis pathway changes in the activities of ALA-D and ALA-S were observed. Such results suggest the possibility of liver impairment of porphyrogenic type as a result of multiple administration of brominated compounds. 

YE X, AL-BABILI s, KLOTZ A, ZHANG J, LUCCA p, BEYER p and POTRYKUS I (2000) Engineering provitamin A ( 3-carotene) biosynthesis pathway into (carotenoid-free) rice endosperm . Science, 287, 303-5. 

Isaacson, T. et al.. Analysis in vitro of the enzyme CRTISO establishes a poly-cis-carotenoid biosynthesis pathway in plants. Plant Physiol. 136, 4246, 2004. 

Bartley, G.E. et al.. Molecular cloning and expression in photosynthetic bacteria of a soybean cDNA coding for phytoene desaturase, an enzyme of the carotenoid biosynthesis pathway, Proc. Natl. Acad. Sci. USA 88, 6532, 1991. 

Hausmann, A. and Sandmann, G., A single five-step desaturase is involved in the carotenoid biosynthesis pathway to beta-carotene and torulene in Neurospora crassa, Eungal Genet. Biol. 30, 147, 2000. 

Strohl, W.R. (2001) Biochemical engineering of natural product biosynthesis pathways. Metabolic Engineering, 3, 4. 

The entire biosynthesis pathway of artemisinin has not been elucidated yet. The first committed step is conversion of FPP to amorphadiene via the cyclization catalyzed by ADS [102] followed by further oxidations of amorphadiene to artemisinic acid. Artemisinic acid can be used as a precursor for semi-synthesis of artemisinin and related chemicals [88]. 

In summary, a novel cyclohexyl avermectin analog B1 with enhanced antiparasitic activity was discovered and produced with high selectivity and excellent fermentation titer through deciphering biosynthesis, pathway engineering, and directed evolution. The new product, doramectin, is sold commercially as Dectomax. 

Several current efforts are focusing on the portability of enzymatic heterocyclization. For example, novel chiral heterocyclic carboxylic acids were produced by using hybrid enzymes [62] (Figure 13.21). Stimulated by biosynthesis pathways, biomimetic heterocyclization methods have also been developed with high efficiency [63]. 

Genes for PHA synthases or entire PHA biosynthesis pathways were identified during cloning by phenotypic complementation. 

There are an overwhelming number of studies which successfully demonstrated heterologous expression of PHA synthesis genes in bacteria it will therefore not be possible to mention them all. Establishment of functional active PHA biosynthesis pathways in E. coli requires not only a PHA synthase but also enzymes that allow the conversion of metabolites, which derive from the provided carbon source, into the R isomers of hydroxyacyl-coenzyme A thioesters that are used as a substrate by the respective PHA synthase. Otherwise, no or only marginal amounts of PHAs are accumulated. 

In addition to the aspects mentioned above, the extent of PHA accumulation might depend on quite different features. The only physiological inhibitor of PHA synthase that has been identified is coenzyme A as pointed out in an earlier section. Since the concentration of coenzyme A in the cytoplasma will probably never rise to very high levels, it may be questionable whether this inhibition is physiologically relevant at all. In our opinion, the availability of a hy-droxyacyl coenzyme A thioester provided by the biosynthesis pathway is most important to initiate PHA biosynthesis (compare also [8] - this book). 

Fig. 5. PHA biosynthesis pathway in recombinant E. coli synthesizing novel PHA with various monomers...

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