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 unfortunately limited.   

Using multiple strategies, Prof. ZHANG Yansheng’s group from the Wuhan Botanical Garden has made significant achievements in increasing the production of betulinic acid in a yeast cell factory. Firstly, they discovered a novel lupeol C-28 oxidase gene from the bark of Betula platyphylla (this gene was designated as BPLO). When the BPLO was applied for the metabolic engineering of betulinic acid production in yeast, it showed a much higher activity than the previously reported lupeol C-28 oxidases, thus dramatically leading to a higher production of betulinic acid in yeast cell. Second, they evaluated two different yeast platforms (WAT11 and CEN.PK) for the production of betulinic acid, and have concluded that the WAT11 strain is better to be used for engineering betulinic acid production. 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. 

This work has been published in BMC Biotechnology entitled “Improvement of betulinic acid biosynthesis in yeast employing multiple strategies”. This project was supported by the National Science and Technology Program of China during the 25th-Year Plan period and the Grant from the Hubei Renyue Pharmaceutical Co., LTD . 

Functional analysis of BPLO by its co-expression with AtLup1 in yeast cells (Image by ZHANG’s group)