Research on Biosynthesis of Anticancer Drug Elemene and Key Enzyme Germacrane A Synthase / 中国生物化学与分子生物学报

ABSTRACT

Elemene is one of the anti-tumor drugs with independent intellectual property rights in China. It has the advantages of strong anti-tumor activity, wide range of action, mild side effects, and resistance to drug resistance, so it is widely used in the clinical treatment of various malignant tumors. The production of elemene mainly relies on the separation and extraction of the medicinal plant Curcuma wenyujin Y. H. Chen & C. Ling. However, the low content of elemene in the natural materials, complex extracting-process, low product-yield, and high cost, that seriously hinder the large-scale production and the application of elemene. With the development of synthetic biology, constructing cell factories to biosynthesize natural medicines has become a research hotspot, which also provides a new approach for the production of elemene. In recent years, the research on the biosynthesis of elemene has continued to deepen. Researchers have tried to clarify the biosynthesis pathway and key enzymes of elemene by means of metabolic engineering, combinatorial biology, genetic engineering. Some key enzyme genes in the biosynthetic pathway of elemene have been successfully cloned, and the heterologous biosynthesis of elemene has been preliminarily realized. This paper summarizes the elemene biosynthesis pathway and the optimization of engineered bacteria with a review of synthetic biology research thinking, and focuses on the key enzyme gemacrane A synthase (GAS). The optimization strategy of elemene biosynthesis is described, including the overexpression of key rate-limiting enzyme genes, the knockout of shunt genes, the enzymes engineering strategy of fusion expression, and in vitro evolution of key enzyme germacrane A synthetase. The problems and challenges faced in improving the yield of elemene in heterologous biosynthesis were also analyzed. The review will provide a reference for the efficient biosynthesis of elemene.