Peppermint produces monoterpenes which are of great commercial value in different traditional and modern pharmaceutical and cosmetic industries. In the classical view, monoterpenes are synthesized via the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, while the cytosolic mevalonate (MVA) pathway produces sesquiterpenes. Interactions between both pathways have been documented in several other plant species, however, a quantitative understanding of the metabolic network involved in monoterpene biosynthesis is still lacking. Isotopic tracer analysis, steady state 13C metabolic flux analysis (MFA) and pathway inhibition studies were applied in this study to quantify metabolic fluxes of primary and isoprenoid metabolism of peppermint glandular trichomes (GT). Our results offer new insights into peppermint GT metabolism by confirming and quantifying the crosstalk between the two isoprenoid pathways towards monoterpene biosynthesis. In addition, a quantitative description of precursor pathways involved in isoprenoid metabolism is given. While glycolysis was shown to provide precursors for the MVA pathway, the oxidative bypass of glycolysis fueled the MEP pathway, indicating prominent roles for the oxidative branch of the pentose phosphate pathway and RuBisCO. This study reveals the potential of 13C-MFA to ascertain previously unquantified metabolic routes of the trichomes and thus advancing insights on metabolic engineering of this organ.

中文翻译：

---

甲羟戊酸途径有助于薄荷中单萜的产生

薄荷生产的单萜在不同的传统和现代制药和化妆品行业中都具有巨大的商业价值。在经典观点中，单萜烯通过质体2-C-甲基-D-赤藓糖醇4-磷酸（MEP）途径合成，而胞质甲羟戊酸酯（MVA）途径产生倍半萜烯。两种途径之间的相互作用已经在其他几种植物中得到了证明，但是，仍然缺乏对涉及单萜生物合成的代谢网络的定量理解。同位素示踪分析，稳态13C代谢通量分析（MFA）和途径抑制研究已用于本研究中，以量化薄荷腺毛（GT）的初级和类异戊二烯代谢的代谢通量。我们的结果通过确认和量化通往单萜生物合成的两种类异戊二烯途径之间的串扰，为薄荷GT代谢提供了新的见解。另外，给出了关于类异戊二烯代谢的前体途径的定量描述。尽管糖酵解被证明为MVA途径提供了前体，但糖酵解的氧化旁路为MEP途径提供了燃料，表明戊糖磷酸途径和RuBisCO的氧化分支发挥了重要作用。这项研究揭示了13C-MFA在确定毛状体先前未量化的代谢途径方面的潜力，从而促进了对该器官代谢工程的认识。给出了涉及类异戊二烯代谢的前体途径的定量描述。尽管糖酵解被证明为MVA途径提供了前体，但糖酵解的氧化旁路为MEP途径提供了燃料，表明戊糖磷酸途径和RuBisCO的氧化分支发挥了重要作用。这项研究揭示了13C-MFA在确定毛状体先前未量化的代谢途径方面的潜力，从而促进了对该器官代谢工程的认识。给出了涉及类异戊二烯代谢的前体途径的定量描述。尽管糖酵解被证明为MVA途径提供了前体，但糖酵解的氧化旁路为MEP途径提供了燃料，表明戊糖磷酸途径和RuBisCO的氧化分支发挥了重要作用。这项研究揭示了13C-MFA可能确定毛状体先前未量化的代谢途径，从而增进了对该器官代谢工程的认识。