A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte Pestalotiopsis microspora, a Taxol Producer
A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte Pestalotiopsis microspora, a Taxol Producer
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紫杉醇生产者内生菌拟盘多毛霉中二苯并二氧辛生物合成的基因簇
DOI：
10.4014/jmb.1905.05051
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发表时间：
2019-10-01
影响因子：
2.8
通讯作者：
Zhu, Xudong
中科院分区：
文献类型：
--
作者：
Liu, Yanjie;Chen, Longfei;Zhu, Xudong
真菌产物二苯并二氧杂环辛酮类有望成为一类新型的胆固醇酯转移蛋白（CEPT）抑制剂。关于它们的生物合成的知识很少。在本报告中，我们表征了另外四种二苯并二氧辛酮类化合物，它们沿着与先前描述的成员pestalotiollide B一起，界定了小孢假单胞菌次级代谢产物的优势谱。通过在g α 1 δ中的mRNA-seq分析，一种停止二苯并二氧杂环辛酮类产生的过程，定义了一个包含21个基因的基因簇，包括一个聚酮合酶，命名为pks 8。簇中基因的破坏导致化合物的损失，从而结束了化学物质生物合成中的预期作用。暂时推测了二苯并二氧杂环辛酮类化合物的生物合成途径。本研究揭示了真菌中二苯并二氧辛酮生物合成的遗传基础，为药物开发竞技场中提高产量提供了依据。
The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in g alpha 1 Delta, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.