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

Biosci Biotechnol Biochem. 2019 Apr;83(4):774-780. doi: 10.1080/09168451.2018.1562880. Epub 2018 Dec 25.

Abstract

Cyclooxygenases are responsible for the production of prostaglandin H2 (PGH2) from arachidonic acid. PGH2 can be converted into some bioactive prostaglandins, including prostaglandin F (PGF), a potent chemical messenger used as a biological regulator in the fields of obstetrics and gynecology. The chemical messenger PGF has been industrially produced by chemical synthesis. To develop a biotechnological process, in which PGF 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 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 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.

Keywords: cyclooxygenase; mediated transformation; prostaglandin F.

MeSH terms

  • Agrobacterium tumefaciens / genetics
  • Agrobacterium tumefaciens / metabolism
  • Algal Proteins / genetics*
  • Algal Proteins / metabolism
  • Arachidonic Acid / metabolism*
  • Culture Media / chemistry
  • Dinoprost / biosynthesis*
  • Gene Expression
  • Gracilaria / chemistry*
  • Gracilaria / genetics
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Metabolic Engineering / methods*
  • Mortierella / genetics*
  • Mortierella / metabolism
  • Mycelium / genetics
  • Mycelium / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Transformation, Genetic
  • Transgenes

Substances

  • Algal Proteins
  • Culture Media
  • Arachidonic Acid
  • Dinoprost
  • Hydroxyprostaglandin Dehydrogenases
  • prostaglandin-F synthase
  • Prostaglandin-Endoperoxide Synthases