Liu Yanbin, Chen Xixian, Zhang Congqiang
Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science Technology and Research (A*STAR), 31 Biopolis Way, Level 6 Nanos building, Singapore 138669, Singapore.
Eng Microbiol. 2022 Nov 10;3(1):100058. doi: 10.1016/j.engmic.2022.100058. eCollection 2023 Mar.
Diterpenes, or diterpenoids, are the most abundant and diverse subgroup of terpenoids, the largest family of secondary metabolites. Most diterpenes possess broad biological activities including anti-inflammatory, antiviral, anti-tumoral, antimicrobial, anticancer, antifungal, antidiabetic, cardiovascular protective, and phytohormone activities. As such, diterpenes have wide applications in medicine (e.g., the anticancer drug Taxol and the antibiotic pleuromutilin), agriculture (especially as phytohormones such as gibberellins), personal care (e.g., the fragrance sclareol) and food (e.g., steviol glucosides as low-calorie sweeteners) industries. Diterpenes are biosynthesized in a common route with various diterpene synthases and decoration enzymes like cytochrome P450 oxidases, glycosidases, and acyltransferases. Recent advances in DNA sequencing and synthesis, omics analysis, synthetic biology, and metabolic engineering have enabled efficient production of diterpenes in several chassis hosts like , and . This review summarizes the recently discovered diterpenes, their related enzymes and biosynthetic pathways, particularly highlighting the microbial synthesis of high-value diterpenes directly from inexpensive carbon sources (e.g., sugars). The high titers (>4 g/L) achieved mean that some of these endeavors are reaching or close to commercialization. As such, we envisage a bright future in translating microbial synthesis of diterpenes into commercialization.
二萜类化合物，即二萜烯，是萜类化合物中含量最为丰富且种类最多的亚类，而萜类化合物是最大的次生代谢产物家族。大多数二萜类化合物具有广泛的生物活性，包括抗炎、抗病毒、抗肿瘤、抗菌、抗癌、抗真菌、抗糖尿病、心血管保护以及植物激素活性。因此，二萜类化合物在医药（如抗癌药物紫杉醇和抗生素截短侧耳素）、农业（特别是作为赤霉素等植物激素）、个人护理（如香料香紫苏醇）和食品（如甜菊糖苷作为低热量甜味剂）行业有着广泛应用。二萜类化合物通过多种二萜合酶以及修饰酶（如细胞色素P450氧化酶、糖苷酶和酰基转移酶）以共同途径进行生物合成。DNA测序与合成、组学分析、合成生物学和代谢工程方面的最新进展使得在几种底盘宿主（如 、 和 ）中能够高效生产二萜类化合物。本综述总结了最近发现的二萜类化合物、它们相关的酶和生物合成途径，特别强调了直接从廉价碳源（如糖类）微生物合成高价值二萜类化合物。所达到的高滴度（>4 g/L）意味着其中一些努力正在接近或已达到商业化水平。因此，我们设想将二萜类化合物的微生物合成转化为商业化有着光明的未来。
