In addition to investigating the effect of differentlength and structure of the linker which attaches BA and NO donor,we also considered the fact that tumor cells display the character of“addicted nitrogen” and increase the transfer rate of amino acids,as a result,we supposed that introducing amino acids into thetarget compounds may enhance their selectivity to tumor cells.
Prof. ZHANG Yansheng and his Ph.D. student HUANG Lili from the Natural Product Biosynthesis Research Group at Wuhan Botanical Garden have isolated two key genes (CrAS and CrAO) involved in the biosynthesis of ursolic- and oleanolic acids from the medicinal plant Catharanthus roseus. When the CrAS and CrAO were co-expressed in yeast cells, the transgenic yeast strains showed the abilities for the de novo biosynthesis of ursolic- and oleanolic acids. The researchers were surprised to find that the CrAO was able to catalyze the synthesis of the anti-cancer compound “betulinic acid” using the lupeol as the substrate. Until now, betulinic acid is mainly originated from the bark of birch tree. It is costly to extract the betulinic acid from the tree directly. Through the unnatural combination of the lupeol synthase gene (AtLUP1) from Arabidopsis thaliana and the CrAO from Catharanthus roseus, the first bio-synthesis of the anti-tumor compound “betulinic acid” in yeast cells was presented.
BIOSYNTHESIS OF LEX FAMILY GLYCOSPHINGOLIPIDS …
Researchers first discovered a novel lupeol C-28 oxidase gene from the bark of (this gene was designated as ). When it was applied for the metabolic engineering of betulinic acid production in yeast, the BPLO showed a much higher activity than the previously reported lupeol C-28 oxidases, leading to a higher production of betulinic acid in yeast cell.
Proteomic Investigation into Betulinic Acid-Induced …
Betulinic acid (BA), as a lupane-type triterpene, shows a wide range of health benefits, especially a selectively inhibitory activity against melanoma cells with no side effects. However, due to its short supply from nature, the commercial application of this drug material is limited.
Based on the WAT11 strain, they performed a chromosome-editing and modified the yeast strain by disrupting the Gal80p gene. Interestingly, the mutant strain improved the biosynthesis of betulinic acid up to 2.2-fold relative to the wild type WAT11 strain.