Applied Microbiology and Biotechnology, Vol.104, No.8, 3339-3348, 2020
Biotechnological production of betulinic acid and derivatives and their applications
Betulinic acid (BA), a lupane-type triterpenoid, mainly distributes in birch plants. It has been reported that BA and its derivatives possess potent anticancer and anti-HIV activities. Commercial production of BA to date depends on phytochemical extraction and semi-synthesis from betulin (a biosynthetic precursor of BA). The biosynthetic pathway of BA has been completely revealed so far. The relevant enzymes involved in BA biosynthesis are summarized in this review. The studies on construction of biotechnological platforms for production of BA and other related triterpenoids are subsequently reviewed. The engineering strategies include overexpression of rate-limiting enzymes of triterpenoid biosynthesis, balancing flux between triterpenoid biosynthetic pathway and others, engineering endoplasmic reticulum, and improving cofactor availability. At the end, this review also attempted to provide future perspectives on potential strategies for further optimizing biosynthesis of BA and other triterpenoids in microbial hosts.