College of Pharmaceutical Sciences , Southwest University , Chongqing 400715 , P. R. China.
Org Lett. 2019 May 3;21(9):3114-3118. doi: 10.1021/acs.orglett.9b00768. Epub 2019 Apr 16.
A new and concise biosynthetic pathway of fungal diphenyl ethers (DPEs) has been elucidated and efficiently reconstructed in yeast. The pathway includes an unusual nonreducing polyketide synthase (NRPKS) responsible for the formation of a polyketide dimer with an ether bond linkage as well as two cofactor-independent enzymes that catalyze tandem regioselective decarboxylation reactions. Our discovery here opens a new window for utilizing fungal DPEs as a platform to design and synthesize analogues for the development of highly useful drug leads.
已阐明并在酵母中有效重建了真菌二苯醚（DPE）的新颖而简洁的生物合成途径。该途径包括一个不寻常的非还原聚酮合酶（NRPKS），负责形成具有醚键连接的聚酮二聚体，以及两个辅因子独立的酶，它们催化串联区域选择性脱羧反应。我们在这里的发现为利用真菌 DPE 作为平台来设计和合成类似物以开发高度有用的药物先导物开辟了新的窗口。
