Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsukacho, Shobara, Hiroshima, 727-0023, Japan.
Appl Biochem Biotechnol. 2021 Nov;193(11):3496-3511. doi: 10.1007/s12010-021-03629-2. Epub 2021 Jul 21.
Plants have evolved a diverse array of secondary metabolite biosynthetic pathways. Undifferentiated plant cells, however, tend to biosynthesize secondary metabolites to a lesser extent and sometimes not at all. This phenomenon in cultured cells is associated with the transcriptional suppression of biosynthetic genes due to epigenetic alterations, such as low histone acetylation levels and/or high DNA methylation levels. Here, using cultured cells of bamboo (Bambusa multiplex; Bm) as a model system, we investigated the effect of histone deacetylase (HDAC) inhibitors on the activation of cryptic secondary metabolite biosynthesis. The Bm suspension cells cultured in the presence of an HDAC inhibitor, suberoyl bis-hydroxamic acid (SBHA), exhibited strong biosynthesis of some compounds that are inherently present at very low levels in Bm cells. Two major compounds induced by SBHA were isolated and were identified as 3-O-p-coumaroylquinic acid (1) and 3-O-feruloylquinic acid (2). Their productivities depended on the type of basal culture medium, initial cell density, and culture period, as well as the SBHA concentration. The biosynthesis of these two compounds was also induced by another HDAC inhibitor, trichostatin A. These results demonstrate the usefulness of HDAC inhibitors to activate cryptic secondary metabolite biosynthesis in cultured plant cells.
植物已经进化出了多种多样的次生代谢物生物合成途径。然而,未分化的植物细胞往往合成次生代谢物的程度较低,有时甚至完全不合成。这种在培养细胞中的现象与由于表观遗传改变(如组蛋白乙酰化水平低和/或 DNA 甲基化水平高)导致的生物合成基因的转录抑制有关。在这里,我们使用竹子(Bambusa multiplex;Bm)的培养细胞作为模型系统,研究了组蛋白去乙酰化酶(HDAC)抑制剂对隐成性次生代谢物生物合成的激活作用。在组蛋白去乙酰化酶抑制剂亚丁基双羟肟酸(SBHA)存在的条件下培养的 Bm 悬浮细胞表现出强烈的一些固有含量非常低的化合物的生物合成。由 SBHA 诱导的两种主要化合物被分离出来,并鉴定为 3-O-对香豆酰奎尼酸(1)和 3-O-阿魏酰奎尼酸(2)。它们的产量取决于基础培养基的类型、初始细胞密度、培养周期以及 SBHA 的浓度。这两种化合物的生物合成也被另一种 HDAC 抑制剂曲古抑菌素 A 诱导。这些结果表明 HDAC 抑制剂在激活培养植物细胞中的隐成性次生代谢物生物合成方面是有用的。