Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, Institute of Biochemistry and Biotechnology, College of Life Sciences, Beijing Normal University, Beijing, 100875, P.R. China.
Zhejiang Medicine Co., Ltd., Zhejiang, P.R. China.
J Microbiol Biotechnol. 2019 Oct 28;29(10):1570-1579. doi: 10.4014/jmb.1905.05051.
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 . Through mRNA-seq profiling in , a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as , 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.
真菌产物二苯并二氧杂环庚酮有望成为一类新型胆固醇酯转移蛋白 (CEPT) 抑制剂。目前对其生物合成知之甚少。在本报告中，我们鉴定了另外四种二苯并二氧杂环庚酮，它们与之前描述的成员 pestalotiollide B 一起，限定了真菌中次级代谢产物的主要谱。通过在真菌中进行 mRNA-seq 分析，该过程阻止了二苯并二氧杂环庚酮的产生，定义了一个包含 21 个基因的基因簇，包括一个多酮合酶，命名为 。该基因簇中基因的破坏导致化合物的丢失，从而得出了它们在这些化合物生物合成中的预期作用。推测了二苯并二氧杂环庚酮的生物合成途径。本研究揭示了真菌中二苯并二氧杂环庚酮生物合成的遗传基础，并可能有助于在药物开发领域提高产量。
