Department of Botany and Plant Pathology, Purdue University, 915 W. State St., West Lafayette, IN, 47907, USA.
Center for Plant Biology, Purdue University, 610 Purdue Mall, West Lafayette, IN, 47907, USA.
Plant J. 2021 Jun;106(6):1605-1624. doi: 10.1111/tpj.15258. Epub 2021 Apr 21.
Endosidin20 (ES20) is a recently identified cellulose biosynthesis inhibitor (CBI) that targets the catalytic site of plant cellulose synthase (CESA). Here, we screened over 600 ES20 analogs and identified nine active analogs named ES20-1 to ES20-9. Among these, endosidin20-1 (ES20-1) had stronger inhibitory effects on plant growth and cellulose biosynthesis than ES20. At the biochemical level, we demonstrated that ES20-1, like ES20, directly interacts with CESA6. At the cellular level, this molecule, like ES20, induced the accumulation of cellulose synthase complexes at the Golgi apparatus and inhibited their secretion to the plasma membrane. Like ES20, ES20-1 likely targets the catalytic site of CESA. However, through molecular docking analysis using a modeled structure of full-length CESA6, we found that both ES20 and ES20-1 might have another target site at the transmembrane regions of CESA6. Besides ES20, other CBIs such as isoxaben, C17, and flupoxam are widely used tools to dissect the mechanism of cellulose biosynthesis and are also valuable resources for the development of herbicides. Here, based on mutant genetic analysis and molecular docking analysis, we have identified the potential target sites of these CBIs on a modeled CESA structure. Some bacteria also produce cellulose, and both ES20 and ES20-1 inhibited bacterial cellulose biosynthesis. Therefore, we conclude that ES20-1 is a more potent analog of ES20 that inhibits intrinsic cellulose biosynthesis in plants, and both ES20 and ES20-1 show an inhibitory effect on bacterial growth and cellulose synthesis, making them excellent tools for exploring the mechanisms of cellulose biosynthesis across kingdoms.
内消旋-20（ES20）是一种最近发现的纤维素生物合成抑制剂（CBI），它靶向植物纤维素合酶（CESA）的催化部位。在这里，我们筛选了超过 600 种 ES20 类似物，并鉴定了 9 种活性类似物，命名为 ES20-1 到 ES20-9。在这些类似物中，内消旋-20-1（ES20-1）对植物生长和纤维素生物合成的抑制作用比 ES20 更强。在生化水平上，我们证明 ES20-1 像 ES20 一样，直接与 CESA6 相互作用。在细胞水平上，这种分子，像 ES20 一样，诱导纤维素合酶复合物在高尔基体中积累，并抑制它们向质膜的分泌。像 ES20 一样，ES20-1 可能靶向 CESA 的催化部位。然而，通过使用全长 CESA6 的模型结构进行分子对接分析，我们发现 ES20 和 ES20-1 可能在 CESA6 的跨膜区域还有另一个靶位。除了 ES20，其他 CBI 如异恶唑草酮、C17 和氟咯草酮等被广泛用于剖析纤维素生物合成机制，也是开发除草剂的宝贵资源。在这里，我们基于突变体遗传分析和分子对接分析，确定了这些 CBI 在模型化 CESA 结构上的潜在靶位。一些细菌也产生纤维素，ES20 和 ES20-1 都抑制细菌纤维素的生物合成。因此，我们得出结论，ES20-1 是 ES20 的一种更有效的类似物，它抑制植物内在的纤维素生物合成，ES20 和 ES20-1 都对细菌生长和纤维素合成有抑制作用，使它们成为探索跨领域纤维素生物合成机制的优秀工具。
