Department of Cellular Biochemistry, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str.3, D-06120 Halle (Saale), Germany; Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, SK-832 32 Bratislava, Slovakia.
Department of Molecular Signal Processing, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany.
J Plant Physiol. 2018 Apr;223:1-8. doi: 10.1016/j.jplph.2018.01.007. Epub 2018 Jan 31.
Benzylisoquinoline alkaloids (BIAs) are important secondary plant metabolites and include medicinally relevant drugs, such as morphine or codeine. As the de novo synthesis of BIA backbones is (still) unfeasible, to date the opium poppy plant Papaver somniferum L. represents the main source of BIAs. The formation of BIAs is induced in poppy plants by stress conditions, such as wounding or salt treatment; however, the details about regulatory processes controlling BIA formation in opium poppy are not well studied. Environmental stresses, such as wounding or salinization, are transduced in plants by phospholipid-based signaling pathways, which involve different classes of phospholipases. Here we investigate whether pharmacological inhibition of phospholipase A (PLA, inhibited by aristolochic acid (AA)) or phospholipase D (PLD; inhibited by 5-fluoro-2-indolyl des-chlorohalopemide (FIPI)) in poppy plants influences wound-induced BIA accumulation and the expression of key biosynthetic genes. We show that inhibition of PLA results in increased morphinan biosynthesis concomitant with reduced production of BIAs of the papaverine branch, whereas inhibition of PLD results in increased production of BIAs of the noscapine branch. The data suggest that phospholipid-dependent signaling pathways contribute to the activation of morphine biosynthesis at the expense of the production of other BIAs in poppy plants. A better understanding of the effectors and the principles of regulation of alkaloid biosynthesis might be the basis for the future genetic modification of opium poppy to optimize BIA production.
苯并异喹啉生物碱（BIAs）是重要的植物次生代谢物，包括具有药用价值的药物，如吗啡或可待因。由于 BIA 骨干的从头合成仍然不可行，迄今为止，罂粟植物 Papaver somniferum L. 仍然是 BIA 的主要来源。BIAs 的形成是由罂粟植物受到胁迫条件诱导的，如创伤或盐处理；然而，关于控制罂粟中 BIA 形成的调节过程的细节尚未得到很好的研究。环境胁迫，如创伤或盐渍化，在植物中通过基于磷脂的信号通路传递，其中涉及不同类别的磷脂酶。在这里，我们研究了在罂粟植物中抑制磷脂酶 A（PLA，被马兜铃酸（AA）抑制）或磷脂酶 D（PLD；被 5-氟-2-吲哚基去氯卤派啶（FIPI）抑制）是否会影响创伤诱导的 BIA 积累和关键生物合成基因的表达。我们表明，抑制 PLA 会导致吗啡生物合成增加，同时降低罂粟碱分支的 BIA 产量，而抑制 PLD 会导致北美黄连分支的 BIA 产量增加。数据表明，磷脂依赖性信号通路有助于激活吗啡生物合成，而牺牲罂粟植物中其他 BIA 的产生。更好地了解生物碱生物合成的效应物和调节原则可能是未来对罂粟进行遗传修饰以优化 BIA 生产的基础。
