Biosynthetic assembly of cytochalasin backbone
Biosynthetic assembly of cytochalasin backbone
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DOI：
10.1016/j.tetlet.2013.03.120
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发表时间：
2013-06-05
影响因子：
1.8
通讯作者：
Oikawa, Hideaki
中科院分区：
文献类型：
--
作者：
Fujii, Ryuya;Minami, Atsushi;Oikawa, Hideaki
鉴于结构多样性和生物活性，细胞松弛素是一类重要的真菌天然产物。尽管它们的生物合成研究已得到广泛研究，但详细的分子组装机制仍有待解决。我们成功在米曲霉中异源表达细胞松弛素聚酮合酶-非核糖体肽合成酶（PKS-NRPS）杂合基因ccsA和反式作用烯酰辅酶A还原酶基因ccsC。所得转化体产生了具有细胞松弛素主链的新型代谢物。这证实了 CcsA 能够与 CcsC 合作构建与苯丙氨酸连接的八酮化合物，并且 CcsA R 结构域催化硫键 PKS-NRPS 产物的还原裂解。 (C) 2013 Elsevier Ltd. 保留所有权利。
Cytochalasins are an important class of fungal natural products in view of structural diversity and biological activities. Although their biosynthetic studies have been examined extensively, the detailed molecular assembly mechanism remains to be solved. We have succeeded to heterologously express the cytochalasin polyketide synthase-non-ribosomal peptide synthetase (PKS-NRPS) hybrid gene ccsA and the trans-acting enoyl-CoA reductase gene ccsC in Aspergillus oryzae. The resultant transformant produced a novel metabolite possessing the cytochalasin backbone. This established that CcsA is capable of constructing the octaketide connected with phenylalanine in collaboration with CcsC, and that CcsA R domain catalyzes reductive cleavage of the thio-tethered PKS-NRPS product. (C) 2013 Elsevier Ltd. All rights reserved.