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. KEY POINTS: • Summarizes the relevant enzymes involved in betulinic acid (BA) biosynthesis. • Highlights recent advances in biotechnological production of BA-related compounds. • Provides future perspectives on strategies for optimizing triterpenoid biosynthesis.

中文翻译：

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桦木酸及其衍生物的生物技术生产及其应用。

桦木酸（BA）是一种羽扇豆型三萜，主要分布于桦树植物中。据报道，BA 及其衍生物具有强大的抗癌和抗 HIV 活性。迄今为止，BA 的商业生产依赖于桦木脑（BA 的生物合成前体）的植物化学提取和半合成。到目前为止，BA的生物合成途径已经完全揭示。本综述总结了参与 BA 生物合成的相关酶。随后回顾了构建用于生产BA和其他相关三萜类化合物的生物技术平台的研究。工程策略包括三萜类生物合成限速酶的过表达、平衡三萜类生物合成途径与其他途径之间的通量、工程化内质网和提高辅因子的可用性。最后，这篇综述还试图为进一步优化微生物宿主中 BA 和其他三萜类化合物的生物合成的潜在策略提供未来的观点。要点： • 总结涉及桦木酸 (BA) 生物合成的相关酶。• 重点介绍 BA 相关化合物生物技术生产的最新进展。• 提供有关优化三萜生物合成策略的未来展望。