Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
CAS Key Laboratory of Green Process and Engineering & State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
Appl Microbiol Biotechnol. 2021 Jun;105(11):4501-4513. doi: 10.1007/s00253-021-11350-7. Epub 2021 May 28.
Terpenoids are natural compounds predominantly present in plants. They have many pharmaceutical and/or nutritional functions, and have been widely applied in medical, food, and cosmetics industries. Recently, terpenoids have been used in the clinical treatment of COVID-19 due to the good antiviral activities. The increasing demand for terpenoids in international markets poses a serious threat to many plant species. For environmentally sustainable development, microbial cell factories have been utilized as the promising platform to produce terpenoids. Nevertheless, the bioproduction of most terpenoids cannot meet commercial requirements due to the low cost-benefit ratio until now. The biosynthetic potential of endophytes has gained attention in recent decades owing to the continual discovery of endophytes capable of synthesizing plant bioactive compounds. Accordingly, endophytes could be alternative sources of terpenoid-producing strains or terpenoid synthetic genes. In this review, we summarized the research progress describing the main and supporting roles of endophytes in terpenoid biosynthesis and biotransformation, and discussed the current problems and challenges which may prevent the further exploitation. This review will improve our understanding of endophyte resources for terpenoid production in industry in the future. The four main research interests on endophytes for terpenoid production. A: Isolation of terpenoid-producing endophytes; B: The heterologous expression of endophyte-derived terpenoid synthetic genes; C: Endophytes promoting their hosts' terpenoid production. The blue dashed arrows indicate signal transduction; D: Biotransformation of terpenoids by endophytes or their enzymes. Key points• The mechanisms employed by endophytes in terpenoid synthesis in vivo and in vitro.• Endophytes have the commercial potentials in terpenoid bioproduction and biotransformation.• Synthetic biology and multiomics will improve terpenoid bioproduction in engineered cell factories.
萜类化合物是主要存在于植物中的天然化合物。它们具有许多药物和/或营养功能,已广泛应用于医学、食品和化妆品行业。最近,由于萜类化合物具有良好的抗病毒活性,因此已将其用于 COVID-19 的临床治疗。国际市场对萜类化合物的需求不断增加,这对许多植物物种构成了严重威胁。为了实现环境可持续发展,微生物细胞工厂已被用作生产萜类化合物的有前途的平台。然而,到目前为止,由于成本效益比低,大多数萜类化合物的生物生产仍无法满足商业需求。由于不断发现能够合成植物生物活性化合物的内生菌,内生菌的生物合成潜力在最近几十年引起了人们的关注。因此,内生菌可以作为萜类化合物产生菌株或萜类化合物合成基因的替代来源。在这篇综述中,我们总结了描述内生菌在萜类化合物生物合成和生物转化中的主要和辅助作用的研究进展,并讨论了可能阻碍进一步开发的当前问题和挑战。这篇综述将提高我们对内生菌资源在未来工业萜类化合物生产中的理解。内生菌在萜类化合物生产中的四个主要研究兴趣。A:萜类化合物产生内生菌的分离;B:内生菌来源的萜类化合物合成基因的异源表达;C:内生菌促进其宿主萜类化合物的生产。蓝色虚线箭头表示信号转导;D:内生菌或其酶对萜类化合物的生物转化。要点• 内生菌在体内和体外萜类化合物合成中采用的机制。• 内生菌在萜类化合物的生物生产和生物转化方面具有商业潜力。• 合成生物学和多组学将提高工程化细胞工厂中萜类化合物的生物生产。