The mevalonate pathway is a well-known metabolic route that provides biosynthetic precursors for myriad isoprenoids. An unexpected variety of the pathway has been discovered from recent studies on microorganisms, mainly on archaea. The most recently discovered example, called the "archaeal" mevalonate pathway, is a modified version of the canonical eukaryotic mevalonate pathway and was elucidated in our previous study using the hyperthermophilic archaeon Aeropyrum pernix. This pathway comprises four known enzymes that can produce mevalonate 5-phosphate from acetyl-CoA, two recently discovered enzymes designated as phosphomevalonate dehydratase and anhydromevalonate phosphate decarboxylase, and two more known enzymes: isopentenyl phosphate kinase and isopentenyl pyrophosphate:dimethylallyl pyrophosphate isomerase. To show its wide distribution in archaea and to confirm if its enzyme configuration is identical among species, the putative genes of a lower portion of the pathway – from mevalonate to isopentenyl pyrophosphate – were isolated from the methanogenic archaeon Methanosarcina mazei, which is taxonomically distant from A. pernix, and were introduced in the engineered Escherichia coli strain that produces lycopene, a red carotenoid pigment. Lycopene production, as a measure of isoprenoid productivity, was enhanced when the cells were grown semi-anaerobically with the supplementation of mevalonolactone, which demonstrates that the archaeal pathway can function in bacterial cells to convert mevalonate into isopentenyl pyrophosphate. Gene deletion and complementation analysis using the carotenogenic E. coli strain suggested that both phosphomevalonate dehydratase and anhydromevalonate phosphate decarboxylase from M. mazei are required for the enhancement of lycopene production.

Importance Two enzymes that have recently been identified from the hyperthermophilic archaeon A. pernix as components of the archaeal mevalonate pathway do not require ATP for their reactions. This pathway, therefore, might consume less energy than other mevalonate pathways to produce precursors for isoprenoids. Thus, the pathway might be applicable to metabolic engineering toward the production of valuable isoprenoids that have applications as pharmaceuticals. The archaeal mevalonate pathway was successfully reconstructed in E. coli cells by introducing several genes from the methanogenic or hyperthermophilic archaeon, which demonstrated that the pathway requires the same components even in distantly related archaeal species and can function in bacterial cells.

甲羟戊酸途径是众所周知的代谢途径，其为多种类异戊二烯提供生物合成的前体。从最近对微生物（主要是古细菌）的研究中发现了该途径的意外变化。最新发现的例子称为“古细菌”甲羟戊酸途径，是经典的真核生物戊酸途径的修饰形式，在我们先前的研究中使用超嗜热古细菌Aeropyrum pernix进行了阐明。。该途径包括四种可从乙酰辅酶A产生甲羟戊酸5磷酸酯的酶，两种最近发现的分别称为磷酸甲羟戊酸脱水酶和脱水甲羟戊酸磷酸酯脱羧酶的酶，以及两种更广为人知的酶：异戊烯基磷酸激酶和焦磷酸异戊烯基：焦磷酸二甲基烯丙基焦磷酸异构酶。要显示在古菌，并确认其广泛分布，如果它的酶的配置是物种，通路的下部的推定基因中相同-对异戊烯基焦磷酸从甲羟戊酸-从产甲烷古细菌中分离甲烷马氏产甲烷球菌，其为从分类学上遥远A. pernix，并被引入工程化的大肠杆菌中。产生番茄红素（一种红色类胡萝卜素色素）的菌株。当细胞通过补充甲羟戊酸内酯半厌氧生长时，作为异戊二烯生产率的衡量标准，番茄红素的产生得以增强，这表明古细菌途径可以在细菌细胞中发挥功能，从而将甲羟戊酸转化为焦磷酸异戊烯基。使用致龋性大肠杆菌菌株进行的基因缺失和互补分析表明，来自马氏甲烷八叠球菌的磷酸甲羟戊酸脱水酶和脱水甲羟戊酸磷酸脱羧酶都是增强番茄红素生产所必需的。

重要性最近从高温嗜生古生芽孢杆菌中鉴定出两种酶作为古细菌甲羟戊酸途径的成分，它们的反应不需要ATP。因此，该途径可能比其他甲羟戊酸途径消耗更少的能量来生产类异戊二烯前体。因此，该途径可能适用于代谢工程，以生产有价值的类异戊二烯，其可用作药物。通过引入产甲烷或嗜热古细菌的几个基因，成功地在大肠杆菌细胞中重建了古细菌的甲羟戊酸途径，这表明该途径即使在远缘的古细菌物种中也需要相同的成分，并且可以在细菌细胞中发挥作用。