VanderMolen Karen M, Darveaux Blaise A, Chen Wei-Lun, Swanson Steven M, Pearce Cedric J, Oberlies Nicholas H
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, North Carolina 27402, United States.
Mycosynthetix, Inc., 505 Meadowlands Drive, Suite 103, Hillsborough, North Carolina 27278, United States.
RSC Adv. 2014 Jan 1;4(35):18329-18335. doi: 10.1039/C4RA00274A.
The use of epigenetic modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, has been explored increasingly as a technique to induce the production of additional microbial secondary metabolites. The application of such molecules to microbial cultures has been shown to upregulate otherwise suppressed genes, and in several cases has led to the production of new molecular structures. In this study, the proteasome inhibitor bortezomib was used to induce the production of an additional metabolite from a filamentous fungus (Pleosporales). The induced metabolite was previously isolated from a plant, but the configuration was not assigned until now; in addition, an analogue was isolated from a degraded sample, yielding a new compound. Proteasome inhibitors have not previously been used in this application and offer an additional tool for microbial genome mining.
作为一种诱导产生更多微生物次级代谢产物的技术，表观遗传修饰剂（如组蛋白脱乙酰酶抑制剂和DNA甲基转移酶抑制剂）的应用已得到越来越多的探索。已证实将此类分子应用于微生物培养可上调原本被抑制的基因，并且在若干情况下已导致产生新的分子结构。在本研究中，蛋白酶体抑制剂硼替佐米被用于诱导丝状真菌（格孢腔菌目）产生一种额外的代谢产物。该诱导产生的代谢产物先前是从一种植物中分离得到的，但直到现在其构型仍未确定；此外，从一个降解样品中分离出了一种类似物，得到了一种新化合物。蛋白酶体抑制剂此前尚未用于此应用，为微生物基因组挖掘提供了一种额外的工具。
