近十年天然产物药物的生物合成研究进展

冯金, 潘海学, 唐功利

Research advances in biosynthesis of natural product drugs within the past decade

Jin FENG, Haixue PAN, Gongli TANG

表1 FDA批准的天然产物药物和半合成药物总结

Table 1 Summary of FDA-approved natural product drugs and semisynthetic drugs

批准药物 药物前体 来源 主要功效 结构类型 批准时间 商品名 参考文献 Natural product drugs: 牛磺酸二醇（taurursodiol）* — Ursusthibetanus antiapoptotic steroid 2022 Relyvrio [23] tapinarof* — Photorhabdusluminescens AhR agonist polyketide 2022 Vtama [24] 雌四醇（estetrol）* — humans hormone regulation steroid 2021 Nextstellis [25] 大麻二酚（cannabidiol）* — Cannabissativa L. analgesic, anticonvulsant polyketide 2018 Epidiolex [26] 血管紧张素（angiotensin）Ⅱ* — humans blood pressure regulation peptide 2017 Giapreza [27] 普拉睾酮（prasterone）* — humans hormone regulation steroid 2016 Intrarosa [28] 曲贝替定（trabectedin）* — CandidatusEndoecteinascidiafrumentensis antitumor non-ribosomal peptide 2015 Yondelis [29] 胆酸（cholic acid）* — animals facilitating fat absorption steroid 2015 Cholbam [30] 去氧胆酸 （deoxycholic acid）* — animals cytolytic agent steroid 2015 Kybella [30] Semisynthetic drugs: 瑞扎芬净（rezafungin）* echinocandin Aspergillusdelacroxii antifungal non-ribosomal peptide 2023 Rezzayo [31] 艾瑞芬净（ibrexafungerp） enfumafungin Hormonemacarpetanum antifungal terpene 2021 Brexafemme [32] 伏环孢素（voclosporin） cyclosporine Beauverianivea calcineurin inhibitor non-ribosomal peptide 2021 Lupkynis [33] 克拉司酮（clascoterone） progesterone humans topical androgen antagonist steroid 2020 Winlevi [34] 青蒿琥酯（artesunate） artemisinin Artemisiaannua antimalarial terpene 2020 Artesunate [35] 乳糖醇（lactitol） lactose animals osmotic laxative sugar alcohol 2020 Pizensy [36] 来法莫林（lefamulin）* pleuromutilin Clitopiluspasseckerianus antibacterial terpene 2019 Xenleta [37] 布瑞诺龙（brexanolone） pregnanolone humans antidepressant steroid 2019 Zulresso [38] 利福霉素 （rifamycin）SV rifamycin B Amycolatopsisrifamycinica antibacterial polyketide 2018 Aemcolo [39] 奥玛环素（omadacycline） tetracyclines Streptomyces antibacterial polyketide 2018 Nuzyra [40] 普拉佐米星（plazomicin） sisomicin Micromonosporainositola antibacterial aminoglycoside 2018 Zemdri [41] 莫昔克丁（Moxidectin） avermectin Streptomycesavermitilis antiparasitic polyketide 2018 Moxidectin [42] 艾拉环素（eravacycline） tetracyclines Streptomyces antibacterial polyketide 2018 Xerava [43] 萨瑞环素（sarecycline） tetracyclines Streptomyces antibacterial polyketide 2018 Seysara [44] 米哚妥林（midostaurin） staurosporine Streptomycesstaurosporeus antineoplastic alkaloid 2017 Rydapt [45] 奥贝胆酸 （obeticholic acid） cholic acid animals FXR agonist steroid 2016 Ocaliva [46] 尿苷三乙酸酯 （uridine triacetate） uridine animals antidote nucleoside 2015 Xuriden [47] 头孢洛扎（ceftolozane） cephalosporin Acremonium antibacterial beta-lactam 2014 Zerbaxa [48] 奥利万星（oritavancin） chloroeremomycin Amycolatopsisorientalis antibacterial glycopeptide 2014 Orbactiv [49] Earlier FDA-approved drugs: 奥利司他（orlistat）* lipstatin Streptomycestoxytricini lipase inhibitor fatty acid 1999 Xenical [50] 依托泊苷（etoposide）* podophyllotoxin Podophyllumhexandrum antitumor lignan 1983 Vepesid [51] 长春花碱（vinblastine）* — Catharanthusroseus antitumor alkaloid 1965 Velban [52] 长春新碱（vincristine）* — Catharanthusroseus antitumor alkaloid 1963 Oncovin [52] 秋水仙碱（colchicine）* — Gloriosasuperba anti-inflammatory alkaloid 1961 Colbenemid [53] 吗啡（morphine）* — Papaversomniferum analgesic alkaloid 1941 Morphine sulfate [54] 可待因（codeine）* — Papaversomniferum analgesic alkaloid 1950 Codeine sulfate [54] 东莨菪碱（scopolamine）* — Solanaceae anticholinergic alkaloid 1979 Transderm Scop [55] 维生素（vitamin）B12* — Archaea, bacteria supplement alkaloid 1942 Cyanocobalamin [56] 紫杉醇（paclitaxel）* — Taxusbrevifolia anticancer terpene 1992 Taxol [57]