Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
J Am Chem Soc. 2013 Mar 20;135(11):4171-4. doi: 10.1021/ja311065v. Epub 2013 Mar 7.
Cyanosporasides are marine bacterial natural products containing a chlorinated cyclopenta[a]indene core of suspected enediyne polyketide biosynthetic origin. Herein, we report the isolation and characterization of novel cyanosporasides C-F (3-6) from the marine actinomycetes Salinispora pacifica CNS-143 and Streptomyces sp. CNT-179, highlighted by the unprecedented C-2' N-acetylcysteamine functionalized hexose group of 6. Cloning, sequencing, and mutagenesis of homologous ~50 kb cyanosporaside biosynthetic gene clusters from both bacteria afforded the first genetic evidence supporting cyanosporaside's enediyne, and thereby p-benzyne biradical, biosynthetic origin and revealed the molecular basis for nitrile and glycosyl functionalization. This study provides new opportunities for bioengineering of enediyne derivatives and expands the structural diversity afforded by enediyne gene clusters.
氰孢菌素是一类海洋细菌天然产物，含有一个疑似烯二炔聚酮生物合成起源的氯化环戊[a]茚核心。本文报道了从海洋放线菌盐单胞菌 CNS-143 和链霉菌 CNT-179 中分离得到的新型氰孢菌素 C-F（3-6），其特征为 6 中前所未有的 C-2' N-乙酰半胱氨酸功能化己糖基团。对这两种细菌中约 50kb 的氰孢菌素生物合成基因簇进行克隆、测序和突变，为氰孢菌素的烯二炔、进而 p-苄基双自由基生物合成起源提供了首个遗传证据，并揭示了腈和糖基化功能化的分子基础。本研究为烯二炔衍生物的生物工程提供了新的机会，并扩展了烯二炔基因簇提供的结构多样性。
