"Glucose and ethanol-dependent transcriptional regulation of the astaxanthin biosynthesis pathway in Xanthophyllomyces dendrorhous"

In this work, we showed that glucose caused transcriptional repression of the three genes involved in the synthesis of astaxanthin from geranylgeranyl pyrophosphate in X. dendrorhous, which correlates with a complete inhibition of pigment synthesis. Strikingly, this regulatory response was completely altered in mutant strains that are incapable of synthesizing astaxanthin. However, we found that addition of ethanol caused the induction of crtYB and crtS gene expression and promoted de novo synthesis of carotenoids. The induction of carotenogenesis was noticeable as early as 24 h after ethanol addition.For the first time, we demonstrated that carbon source-dependent regulation of astaxanthin biosynthesis in X. dendrorhous involves changes at the transcriptional level. Such regulatory mechanism provides an explanation for the strong and early inhibitory effect of glucose on the biosynthesis of this carotenoid.Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a red-orange carotenoid pigment of high commercial interest, mainly because of its use as a dietary additive in the aquaculture industry [1,2] and its many benefits to human health [3]. As further properties of this carotenoid have been discovered, demand has increased significantly, thus motivating the identification of new sources of the pigment as an alternative to its chemical synthesis. One of the most promising natural sources of astaxanthin is the basidiomycete yeast Xanthophyllomyces dendrorhous. This yeast normally produces the pigment in its natural environment, probably to protect itself from other chemical compounds. Carotenoids are potent antioxidants, and the main function of astaxanthin in X. dendrorhous has been proposed to be protection against reactive oxygen species and accompanying cellular damage. This hypothesis is supported by the observations that X. dendrorhous is particularly susceptible to some activated oxygen species, has low levels of catalase activity and possesses Mn-superoxid