Effects of arachidonic acid concentration on prostaglandin biosynthesis and feasibility of semibatch processes

The reaction characteristics of prostaglandin E2 biosynthesis by PGH-synthase and PGE2 isomerase and the substrate dependency of this biosynthesis were studied. The activity of PG-synthases was blocked by the inhibitory action of one or more byproducts, probably resulting from the action of PGH-synthase. This inhibitory action then appeared to be partly reversible, indicating that the substrate and the inhibitor compete for the catalytic sites. According to these findings, the feasibility of a successful semibatch biosynthesis was investigated. A combination of the substrate concentration reducing procedure and the semibatch process resulted in an about 3.5-fold higher increase in the total amount of PGE2 formed in comparison with the batch results obtained at the substrate concentration of 1.0 mg/cm3. Since the cost of enzyme is a governing factor in this biosynthesis, development of semibatch biosynthesis of PGE2 becomes a matter of economic importance.