Production of prostaglandin F 2α by molecular breeding of an oleaginous fungus Mortierella alpina.

Cyclooxygenases are responsible for the production of prostaglandin H ₂ (PGH ₂ ) from arachidonic acid. PGH ₂ can be converted into some bioactive prostaglandins, including prostaglandin F _2α (PGF _2α ), a potent chemical messenger used as a biological regulator in the fields of obstetrics and gynecology. The chemical messenger PGF _2α has been industrially produced by chemical synthesis. To develop a biotechnological process, in which PGF _2α can be produced by a microorganism, we transformed an oleaginous fungus, Mortierella alpina 1S-4, rich in triacylglycerol consisting of arachidonic acid using a cyclooxygenase gene from a red alga, Gracilaria vermiculophylla. PGF _2α was accumulated not only in the mycelia of the transformants but also in the extracellular medium. After 12 days of cultivation approximately 860 ng/g and 6421 µg/L of PGF _2α were accumulated in mycelia and the extracellular medium, respectively. The results could facilitate the development of novel fermentative methods for the production of prostanoids using an oleaginous fungus.