基于生物合成和合成化学的天然产物药物发现和衍生
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- 英文论文题名：Natural product discovery and diversification from biosynthesis to semi-synthesis
- 论文作者：梁昊雨 ; 邱林 ; 石俊 ; 蒋林 ; 潘建 ; 朱湘成 ; 沈奔 ; 段燕文 ; 黄勇
- 英文论文作者：HY Liang ; L Qiu ; J Shi ; L Jiang ; J Pan ; B Shen ; YW Duan ; Y Huang ; Xiangya International Academy of Translational Medicine and Xiangya Hospital ; Central South University ; National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery ; Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery ; Departments of Chemistry ; Molecular Therapeutics ; and Natural Products Library Initiative at The Scripps Research Institute
- 年：2016
- 作者机构：中南大学湘雅国际转化医学联合研究院,中南大学湘雅医院,新药组合生物合成国家地方联合工程研究中心,组合生物合成与天然产物药物湖南省工程研究中心;Departments of Chemistry,Molecular Therapeutics,and Natural Products Library Initiativeat The Scripps Research Institute;
- 论文关键词：平板霉素 ; 平板素 ; 雷纳霉素 ; 维吉尼亚霉素M ; bacillaene
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：TQ464
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：117k
- 原文格式：D
- 会议级别：全国
摘要
癌症和感染性疾病严重地危害着我国及世界人民的健康。天然产物是抗癌和抗感染药物的主要来源。随着人们对天然产物生物合成途径研究的不断深入,以及基因组挖掘等技术的应用,天然产物药物开发的又一个黄金时期已经来临。通过对微生物菌株进行生物合成基因扫描,首先确定其是否有产生某类天然产物的潜力,再针对性地进行天然产物分离,将加速天然产物的发现;天然产物的产量可以进一步通过应用合成生物学技术和发酵工程快速提高,为下一步天然产物衍生化,增加其结构多样性奠定坚实的基础。我们将讨论如何综合应用上述方法,开展对被誉为"本世纪抗生素发现里程碑"的平板霉素(platensimycin)和平板素(platencin),结构新奇、抗肿瘤活性优异的雷纳霉素(leinamycin),以及抗生素维吉尼亚霉素M(virginiamycin M)和极其不稳定的抗生素bacillaene的初步研究工作。
Natural products remain the main source of anticancer and anti-infective drugs.A new golden era of natural product discovery is coming,with the remarkable progress in deciphering how natural products are biosynthesized in the past two decades and the application of contemporary natural product discovery approaches,such as genome mining.Many,including us,have envisioned that targeted natural product discovery could be streamlined by firstly identifying the genes encoding natural product biosynthesis in the microbial strains through genome mining approaches.The rapid improvement of natural product yield could further be achieved through the application of synthetic biology and fermentation engineering,thus pave the way for their diversification through semi-synthesis.Several examples from our current efforts by utilizing the above approaches,including the potent antibiotics platensimycin and platencin,antitumor antibiotic leinamycin,antibiotic virginiamycin M and the highly unstable antibiotic bacillaene,would be discussed.
Natural products remain the main source of anticancer and anti-infective drugs.A new golden era of natural product discovery is coming,with the remarkable progress in deciphering how natural products are biosynthesized in the past two decades and the application of contemporary natural product discovery approaches,such as genome mining.Many,including us,have envisioned that targeted natural product discovery could be streamlined by firstly identifying the genes encoding natural product biosynthesis in the microbial strains through genome mining approaches.The rapid improvement of natural product yield could further be achieved through the application of synthetic biology and fermentation engineering,thus pave the way for their diversification through semi-synthesis.Several examples from our current efforts by utilizing the above approaches,including the potent antibiotics platensimycin and platencin,antitumor antibiotic leinamycin,antibiotic virginiamycin M and the highly unstable antibiotic bacillaene,would be discussed.
引文
[1]Shen,B.A new golden age of natural products drug discovery.Cell 2015,163:1297.