Ge Xiangyu, Shi Shepo, Wang Juan
Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Sheng Wu Gong Cheng Xue Bao. 2023 Sep 25;39(9):3605-3614. doi: 10.13345/j.cjb.221006.
Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete IFM 0406 with highly potent immunosuppressive activity (=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.
巴西卡地菌素A（BraA）是一种从致病放线菌IFM 0406中分离出的天然二萜糖苷，具有高效的免疫抑制活性（=0.057μg/mL）。BraA能有效抑制作为T细胞氨基酸转运系统L底物的氨基酸摄取，这与现有的临床免疫抑制剂不同。与已知的临床免疫抑制剂如环孢素A、子囊霉素和他克莫司相比，BraA在小鼠混合淋巴细胞反应中更有效，对各种人类细胞系的毒性更小。因此，BraA作为一种有前景的新型免疫抑制剂受到了更多关注。然而，由于BraA具有不寻常且合成具有挑战性的骨架，并且在天然致病生产菌中产量较低，迄今为止，这种有前景的免疫抑制剂作为医用药物的开发受到阻碍。本综述介绍了BraA的分子结构、活性、作用机制、BraA类似物的化学合成、基因簇的异源表达以及微生物与化学合成相结合生产BraA的应用，旨在促进BraA及其类似物的高效生产。
