Prostaglandin production by the microalga with heterologous expression of cyclooxygenase

Abstract

Prostaglandins (PGs) are the physiologically active compounds synthesized from C20 polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) and a series of PG synthases, and are utilized as pharmaceuticals. Currently, commercialized PGs are mainly produced by chemical synthesis under harsh conditions. By contrast, bioproduction of PGs can be an alternative, environmental-friendly, and inexpensive process with genetic engineering of model plants, although these conventional host organisms contain a limited quantity of PG precursors. In this study, we established an efficient PG production process using the genetically engineered microalga Fistulifera solaris which is rich in C20 PUFAs. A cox gene derived from the red alga Agarophyton vermiculophyllum was introduced into F. solaris. As a result, a transformant clone with high cox expression produced PGs (i.e., PGD 2 , PGE 2 , PGF 2α , and 15-ketoPGF 2α derived from arachidonic acid, and PGD 3 , PGE 3 , and PGF 3α derived from eicosapentaenoic acid) as revealed by liquid chromatography/mass spectrometry. The total content of PGs was 1290.4 ng/g of dry cell weight, which was higher than that produced in the transgenic plant reported previously.The results obtained in this study indicate that the C20 PUFA-rich microalga functionally expressing COX is a promising host for PG bioproduction.

Recent Advances in the Heterologous Expression of Biosynthetic Gene Clusters for Marine Natural Products

“…Using marine microalgae as host strains, several studies have heterologously expressed the genes encoding key enzymes in the biosynthetic pathways of terrestrial plants [ 109 , 110 , 111 ]. For the exploration of MNPs, Maeda [ 83 ] inserted a cox gene derived from a red alga into a genetically engineered microalgal host Fistulifera solaris . The cox gene encoded the biosynthesis of cyclooxygenase.…”