Li Shengying, Anand Krithika, Tran Hong, Yu Fengan, Finefield Jennifer M, Sunderhaus James D, McAfoos Timothy J, Tsukamoto Sachiko, Williams Robert M, Sherman David H
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Medchemcomm. 2012 Aug;3(8):987-996. doi: 10.1039/C2MD20029E.
The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/(-)-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.
具有广泛生物活性的真菌双环[2.2.2]二氮杂辛烷吲哚生物碱的生物合成已引起越来越多的关注。长期以来，人们一直认为它们有趣的组装方式具有非核糖体肽合成酶、一种假定的分子内双烯丙基酶、不同数量的异戊烯基转移酶以及一系列负责对其基于环二肽的结构核心进行各种修饰的氧化酶。直到最近，由于缺乏关于真菌来源的生物合成基因簇的信息，这些生物合成途径的细节在很大程度上仍然未知。在此，我们报告了对一组选定的双环[2.2.2]二氮杂辛烷吲哚生物碱（包括(+)/(-)-诺托酰胺、对赫克酰胺和马尔布兰奇酰胺）的四个天然产物代谢系统的比较分析，其中我们基于深入注释和正在进行的生化研究为生物合成途径中的每一步提出了一种酶。
