Plant Research Laboratory, College of Natural Science, Michigan State University, East LansingMichigan48824, United States.
Department of Chemistry and Biochemistry, California State University, Fullerton, Fullerton, California92831, United States.
J Phys Chem B. 2023 Feb 9;127(5):1144-1157. doi: 10.1021/acs.jpcb.2c07209. Epub 2023 Jan 30.
Plants synthesize small molecule diterpenes composed of 20 carbons from precursor isopentenyl diphosphate and dimethylallyl disphosphate, manufacturing diverse compounds used for defense, signaling, and other functions. Industrially, diterpenes are used as natural aromas and flavoring, as pharmaceuticals, and as natural insecticides or repellents. Despite diterpene ubiquity in plant systems, it remains unknown how plants control diterpene localization and transport. For many other small molecules, plant cells maintain transport proteins that control compound compartmentalization. However, for most diterpene compounds, specific transport proteins have not been identified, and so it has been hypothesized that diterpenes may cross biological membranes passively. Through molecular simulation, we study membrane transport for three complex diterpenes from among the many made by members of the family to determine their permeability coefficient across plasma membrane models. To facilitate accurate simulation, the intermolecular interactions for leubethanol, abietic acid, and sclareol were parametrized through the standard CHARMM methodology for incorporation into molecular simulations. To evaluate the effect of membrane composition on permeability, we simulate the three diterpenes in two membrane models derived from sorghum and yeast lipidomics data. We track permeation events within our unbiased simulations, and compare implied permeation coefficients with those calculated from Replica Exchange Umbrella Sampling calculations using the inhomogeneous solubility diffusion model. The diterpenes are observed to permeate freely through these membranes, indicating that a transport protein may not be needed to export these small molecules from plant cells. Moreover, the permeability is observed to be greater for plant-like membrane compositions when compared against animal-like membrane models. Increased permeability for diterpene molecules in plant membranes suggest that plants have tailored their membranes to facilitate low-energy transport processes for signaling molecules.
植物从异戊烯二磷酸和二甲基烯丙基二磷酸前体合成由 20 个碳原子组成的小分子二萜，制造用于防御、信号传递和其他功能的各种化合物。在工业上，二萜类化合物用作天然香料和调味剂、药物以及天然杀虫剂或驱虫剂。尽管二萜类化合物在植物系统中普遍存在，但仍不清楚植物如何控制二萜类化合物的定位和运输。对于许多其他小分子，植物细胞维持控制化合物区室化的转运蛋白。然而，对于大多数二萜类化合物，尚未鉴定出特定的转运蛋白，因此有人假设二萜类化合物可能被动地穿过生物膜。通过分子模拟，我们研究了来自 科的许多成员产生的三种复杂二萜在质膜模型中的跨膜运输，以确定它们穿过质膜模型的渗透率系数。为了便于准确模拟，通过标准 CHARMM 方法对 leubethanol、abietic acid 和 sclareol 的分子间相互作用进行参数化，以便纳入分子模拟。为了评估膜组成对渗透性的影响，我们在两个源自高粱和酵母脂质组学数据的膜模型中模拟了这三种二萜。我们在无偏模拟中跟踪渗透事件，并将隐含渗透率与使用非均相溶解度扩散模型的 Replica Exchange Umbrella Sampling 计算得出的渗透率进行比较。观察到二萜类化合物自由地透过这些膜渗透，这表明从植物细胞中输出这些小分子可能不需要转运蛋白。此外，与动物样膜模型相比，植物样膜组成的渗透性更高。植物膜中二萜类分子的通透性增加表明，植物已经对其膜进行了调整，以促进信号分子的低能量运输过程。
