A novel retinoic acid analogue, 7-hydroxy retinoic acid, isolated from cyanobacteria

All-trans retinoic acid (RA) is a low-molecular compound derived from vitamin A. It induces events in various ways by binding with the retinoic acid receptor (RAR), a nuclear receptor, in animal cells. RA and its metabolites have been found in animal tissues. In this paper, we report a novel RA analogue found in cyanobacterial cells, describe the method for its isolation, and compare its photo-stability with that of all-trans RA.

The new A analogue was extracted from cells of Microcystis aeruginosa and Spirulina sp. and fractionated by high-performance liquid chromatography. The analogue was analysed using a yeast two-hybrid assay method to measure in vitro RAR-agonistic activity. Liquid chromatography-mass spectrometry/mass spectrometry analyses was performed to elucidate the chemical structure of this RA analogue.

The results of the analysis of the fragments revealed that the novel RA analogue was 7-hydroxy RA. The yields from 3.5 μg (4.5% of the total RAR-agonistic activity of Spirulina sp. cells) of 7-hydroxy RA was a mixture of 4 isomers due to cis-trans isomerisation coupled with keto-enol tautomerism; its relative RAR agonistic activity was 0.49 ± 0.01 (n=3) when the activity of all trans RA was set up to 1.00. Under fluorescent light, the mixture of 7-hydroxy RA isomers was more stable than all- trans RA.

We isolated a novel RAR-activating compound, 7-hydroxy RA, from cyanobacteria.

7-hydroxy RA is more stable than all-trans RA under UV-A.