Isoprenoids compartmentation

A good example of compartmentation, although not yet completely understood, is the apparent segregation of isoprenoid biosynthesis in plants (123). [2- 14C]-Mevalonate was easily incorporated in squalene, phytosterols, P-amyrin and ubiquinone but not in the plastid constituents P-carotene, chlorophyll phytyl group or plastoquinone. The opposite result was obtained with 14C02. 

Acetyl-CoA has already been mentioned as a key precursor for many industrially relevant compounds. For example, it is a direct precursor for the mevalonate pathway to obtain isoprenoids. It is also a key precursor for malonyl-CoA, yielding the production of fatty acids (biodiesel) and polyketides [19]. The challenge of engineering the acetyl-CoA availability in yeast lies in its compartmentalization. While acetyl-CoA is readily available in the mitochondrium, the cytosolic pool is low. The cytosolic pool of acetyl-CoA is fed from acetate, which is activated by a bond to coenzyme A at the expense of 1 ATP. It becomes therefore obvious that any metabolic pathway using cytosolic acetyl-CoA aiming at mass production is energetically detrimental and inefficient - if not recombinantly redesigned [20]. 

Recently, evidence has accumulated based on isotope labeling and feeding experiments that there must be an alternative pathway in some organisms for the formation of the isoprenoid building blocks [96-98]. Initially, it was proposed that distinct and compartmentalized acetyl CoA pools could account for the anomalous labeling patterns observed that were inconsistent with those expect-... 

Figure 3.30 Compartmentation of sesquiterpene biosynthesis in chamomile as proposed by Adam etal. (1 999). Blocks represent isoprenoid precursor units (IPP or DMAPP).

Fig. 5. Isoprenoid and a-cyclopiazonic acid branch points (a) S and T competing for one pool of DMAPP (b) compartmentation of DMAPP into two pools.

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