Biotechnological production of betulinic acid and derivatives and their applications

被引：30

作者：

An, Tianyue ^{[1
,2
]}

Zha, Wenlong ^{[1
,2
]}

Zi, Jiachen ^{[1
,2
]}

机构：

[1] Jinan Univ, Biotechnol Inst Chinese Mat Med, Guangzhou 510632, Peoples R China

[2] Jinan Univ, Coll Pharm, Guangzhou 510632, Peoples R China

来源：

APPLIED MICROBIOLOGY AND BIOTECHNOLOGY | 2020年 / 104卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Betulinic acid; Triterpenoid biosynthesis; Lupeol synthases; Cytochrome P450 enzymes; Metabolic engineering; MULTIFUNCTIONAL TRITERPENE SYNTHASE; SACCHAROMYCES-CEREVISIAE; OXIDOSQUALENE CYCLASES; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; DIRECTED EVOLUTION; BIOSYNTHESIS; OXIDATION; APOPTOSIS; NADPH;

D O I：

10.1007/s00253-020-10495-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：3339 / 3348

页数：10

共 82 条

[1] ENZYMATIC CYCLIZATION OF SQUALENE AND OXIDOSQUALENE TO STEROLS AND TRITERPENES [J].