Pal

Cinnamate

Rosmarinic acid Phenolic-

Phenylpropanoid pathway

Lignin

Figure 3. Proline-linked pentose phosphate pathway. TCA, tricarboxylic acid; PAL, phenylalanine ammonia lysase.

cells (44), differentiating animal tissues (45), and plant tissues (46). The hypothesis of this model is that the same metabolic flux from overexpression of the proline-linked pentose phosphate pathway regulates the interconversion of ribose-5-phosphate to the erythrose-4-phosphate-driving shikimate pathway. Shikimate pathway flux is critical for both auxin and phenylpropanoid biosynthesis, including RA. This hypothesis has been strengthened by preliminary results in which in several oregano clonal lines, RA biosynthesis was significantly stimulated by exogenous addition of A-2-C and ornithine (47). Such clonal lines are also tolerant to Pseudomonas spp. and respond to the bacterium by increasing RA and proline biosynthesis (34,48). High RA-producing clonal lines selected based on the model in this proposal will be targeted for preliminary characterization of key enzymes mentioned earlier. Such genetically uniform clonal lines will also be targeted for developing gene transformation techniques usingAgro&ac-terium or particle gun bombardment. The success of this strategy will lead to access of critical interlinking metabolic pathways associated with RA biosynthesis. This will allow more detailed analysis that will lead to metabolic engineering for efficient RA biosynthesis. This strategy for RA biosynthesis can be the foundation for metabolic engineering of other phytopharmaceuticals from cross-pollinating, heterogeneous species.

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