Department of Bioscience, Nagahama Institute of Bioscience and Technology, 1266 Tamura, Nagahama, Shiga, 526-0829 Japan.
Transborder Medical Research Center, Tsukuba University, 1-1-1 Tenmondai, Tsukuba, Ibaragi, 305-8577 Japan.
Plant Cell Physiol. 2023 Dec 21;64(12):1551-1562. doi: 10.1093/pcp/pcad116.
Folate, also known as vitamin B9, is an essential cofactor for a variety of enzymes and plays a crucial role in many biological processes. We previously reported that plastidial folate prevents starch biosynthesis triggered by the influx of sugar into non-starch-accumulating plastids, such as etioplasts, and chloroplasts under darkness; hence the loss of plastidial folate induces the accumulation of starch in plastids. To understand the molecular mechanism underlying this phenomenon, we screened our in-house chemical library and searched their derivatives to identify chemicals capable of inducing starch accumulation in etioplasts. The results revealed four chemicals, compounds #120 and #375 and their derivatives, compounds #120d and #375d, respectively. The derivative compounds induced starch accumulation in etioplasts and suppressed hypocotyl elongation in dark-grown Arabidopsis seedlings. They also inhibited the post-germinative growth of seedlings under illumination. All four chemicals contained the sulfonamide group as a consensus structure. The sulfonamide group is also found in sulfa drugs, which exhibit antifolate activity, and in sulfonylurea herbicides. Further analyses revealed that compound #375d induces starch accumulation by inhibiting folate biosynthesis. By contrast, compound #120d neither inhibited folate biosynthesis nor exhibited the herbicide activity. Protein and metabolite analyses suggest that compound #120d abrogates folate-dependent inhibition of starch accumulation in etioplasts by enhancing starch biosynthesis.
叶酸，也被称为维生素 B9，是多种酶的必需辅助因子，在许多生物过程中发挥着关键作用。我们之前报道过，质体叶酸可以防止糖流入非淀粉质积累质体（如黄化质体和叶绿体）中所触发的淀粉生物合成；因此，质体叶酸的丧失会导致质体中淀粉的积累。为了了解这一现象的分子机制，我们筛选了我们的内部化学文库，并搜索了它们的衍生物，以鉴定能够在黄化质体中诱导淀粉积累的化学物质。结果发现了四种化学物质，化合物 #120 和 #375 及其衍生物，化合物 #120d 和 #375d。这两种衍生物均能诱导黄化质体中淀粉的积累，并抑制黑暗条件下生长的拟南芥幼苗下胚轴的伸长。它们还抑制了光照下幼苗的出芽后生长。这四种化学物质都含有磺酰胺基作为共识结构。磺酰胺基也存在于磺胺类药物中，它们具有抗叶酸活性，也存在于磺酰脲类除草剂中。进一步的分析表明，化合物 #375d 通过抑制叶酸生物合成诱导淀粉积累。相比之下，化合物 #120d 既不抑制叶酸生物合成，也不表现出除草剂活性。蛋白质和代谢物分析表明，化合物 #120d 通过增强淀粉生物合成来破坏质体中叶酸依赖性的淀粉积累抑制。
