Monoterpenoids are an important subclass of terpenoids that play important roles in the energy, cosmetics, pharmaceuticals, and fragrances fields. With the development of biotechnology, microbial synthesis of monoterpenoids has received great attention. Yeasts such Saccharomyces cerevisiae and Yarrowia lipolytica are emerging as potential hosts for monoterpenoids production because of unique advantages including rapid growth cycles, mature gene editing tools, and clear genetic background. Recently, advancements in metabolic engineering and fermentation engineering have significantly enhanced the accumulation of monoterpenoids in cell factories. First, this review introduces the biosynthetic pathway of monoterpenoids and comprehensively summarizes the latest production strategies, which encompass enhancing precursor flux, modulating the expression of rate-limited enzymes, suppressing competitive pathway flux, mitigating cytotoxicity, optimizing substrate utilization, and refining the fermentation process. Subsequently, this review introduces four representative monoterpenoids. Finally, we outline the future prospects for efficient construction cell factories tailored for the production of monoterpenoids and other terpenoids.

Clover and lemongrass essential oils of contrasting composition, at three concentration levels (1%, 5%, 10%), were administrated via prophylactic and therapeutic inhalation to scopolamine-treated mice. Chemical analysis showed that clover oil was dominant in eugenol (47.69%) and lemongrass free of eugenol but mainly containing monoterpenoids of comparable proportions. Animal behavioural and brain biochemical tests showed that injection of scopolamine caused memory and learning deficit in mice while prophylactic and therapeutic inhalation of two oils at moderate to high concentrations all obviously reversed the cognitive impairment via inhibiting acetylcholinesterase activities, oxidation and inflammation. Lemongrass essential oil with diverse monoterpenoids can be as effective as or a little bit more potent than eugenol-rich clover essential oil possibly due to the synergistic effect of various monoterpenoids. These findings implied that sniffing of such aroma recipes could be a promising complementary approach for the mitigation of Alzheimer\'s disease-related cognitive impairment.

Twenty-four monoterpenoids, including three previously undescribed compounds (1-3), were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). Their structures were unambiguously established based on spectroscopic analysis (HR-ESIMS, IR, 1D, and 2D NMR), and the absolute configurations of 1-3 were elucidated by comparing their experimental and calculated electronic circular dichroism spectra. In addition, the structure of 8 was confirmed by single-crystal X-ray diffraction. The inhibitory activities of 1-24 against neutrophil elastase, 5-lipoxygenase, and cyclooxygenase-2 (COX-2) were studied in vitro for the first time, and the results showed that compound 24 possessed a significant inhibitory effect on COX-2 with an IC50 value of 1.53 ± 0.10 μΜ. This research first reported the presence of monoterpenoids in Acanthopanacis Cortex, including one monoterpenoid 2 with an unusual 4/5 bicyclic lactone system, and compounds 4 and 5 have never been reported in nature.

The use of essential oils derived from the camphor tree to repel mosquitoes is an ancient practice that originated in Southeast Asia and gradually spread to China and across Europe via the Maritime Silk Road. The olfactory mechanisms by which these oils elicit avoidance behavior are unclear. Here we show that plant bicyclic monoterpenoids and borneol specifically activate a neural pathway that originates in the orphan olfactory receptor neuron of the capitate peg sensillum in the maxillary palp, and projects to the mediodorsal glomerulus 3 in the antennal lobe. This neuron co-locates with two olfactory receptor neurons tuned to carbon dioxide and octenol that mediate human-host detection. We also confirm that borneol elicits repellency against human-seeking female mosquitoes. Understanding the functional role of the mosquito maxillary palp is essential to investigating olfactory signal integration and host-selection behavior.

Food security is an important basis and guarantee to national safety, the loss caused by storage pests was a serious problem which affects the food security widely. Frequent application of chemical pesticides caused several critical crises including the development of resistance, pesticide residues, environmental pollution, and exposure risk to human or non-target organisms. The utilization of volatile components acts as a natural alternative for controlling storage pests has aroused extensive interest in recent years. It has been reported that terpinene-4-ol and limonene showed significant insecticidal activity against Sitophilus zeamais in our previous studies, which was evaluated to have strong influences to CYP450 genes. To determine the links and roles of related genes, we identified the SzCYP6MS subfamily genes which encoded a putative protein of 493 or 494 amino acids. Then, the expression of four CYP6MS subfamily genes were increased significantly under the fumigation stress by terpinen-4-ol and limonene, which was determined by the RT-qPCR analysis compared with non-fumigated colonies. In addition, we determined that RNAi-mediated CYP6MS genes knockdown significantly increased the sensitivity of S. zeamais to terpinen-4-ol and limonene, the mortality rates of insects with knocked down CYP6MS1, CYP6MS5, CYP6MS6, CYP6MS8, and CYP6MS9 genes increased by 25%, 25%, 16%, 17%, and 4% in terpinen-4-ol treatment groups and by 29%, 25%, 15%, 22%, and 3% in limonene treatment groups compared with that in the control groups, respectively. Finally, it was validated that CYP6MS5 exhibited the most stable binding with terpinen-4-ol that was similar to the result between CYP6MS8 and limonene which were verified by molecular docking analysis. In together, this study demonstrates the potential of terpinen-4-ol and limonene used as novel botanical pesticides to control storage pests, thereby reducing application of chemical pesticides and postponing resistance development.

BACKGROUND: Methyl jasmonate has an important effect on the synthesis of plant secondary metabolites. Schizonepeta tenuifolia Briq. has a wide range of pharmacological effects and the secondary metabolites are dominated by monoterpenes (pulegone, menthone).
OBJECTIVE: It is essential to determine the changes in secondary metabolites in S. tenuifolia under methyl jasmonate treatment and to probe the molecular mechanism. This can improve the accumulation of secondary metabolites in the medicinal plant S. tenuifolia and enrich the information gene expression at different MeJA levels, which can help to elucidate the molecular mechanism of monoterpenoid synthesis in S. tenuifolia.
METHODS: In this study, we determined the changes in the content of monoterpenoids in S. tenuifolia under methyl jasmonate treatment. Meanwhile, we established a transcriptome database of S. tenuifolia under methyl jasmonate level using high-throughput sequencing.
RESULTS: A certain concentration of MeJA promoted the accumulation of monoterpenoids in S. tenuifolia. The transcriptome database of S. tenuifolia leaves under 0, 50, 100 and 250 μM MeJA treatment was established. We generated 88,373 unigenes with an N50 length of 2678 bp, of which 50,843 (57.53%) can be annotated in at least one database. Compared with the CK (0 μM) group, 12,557 (50 μM), 15,409 (100 μM) and 13,286 (250 μM) differentially expressed genes were identified. GO and KEGG enrichment analysis revealed that JA signal transduction and monoterpenoid synthesis were the two most significant enrichment pathways. The expression levels of related DEGs involved in JA signaling and monoterpenoid synthesis were significantly up-regulated by MeJA. In addition, our phenotypic and differentially expressed gene association analysis revealed that monoterpenoid biosynthesis in S. tenuifolia was more associated with genes involved in plant trichome branching, phytohormone signaling and transcriptional regulation.
CONCLUSIONS: This study confirmed that methyl jasmonate significantly promoted monoterpenoid biosynthesis in S. tenuifolia. A large number of genes responding to methyl jasmonate were associated with JA signaling and monoterpenoid biosynthesis.

Six undescribed monoterpenoids, together with twelve known compounds were isolated and identified from Hyssopus cuspidatus Boriss. Their structures were established by spectroscopic analysis, and the absolute configurations were established by ECD calculations and single-crystal X-ray diffraction crystallography. The isolated compounds were tested for their anti-inflammatory, antibacterial and antitumor activities. Most of the compounds showed potent anti-inflammatory activities. Among them, 3β-hydroxy-7,8-dihydro-β-ionone (8), oleanolic acid (17) and acetylpleamolic acid (18) showed strong anti-inflammatory activity against IL-6 and TNF-α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Several compounds showed moderate inhibitory activities against Staphylococcus aureus, Candida albicans, and Escherichia coli. And (4S)-p-menth-l-ene-7,8-diol 8-O-β-D-glucopyranoside (16) showed antitumor activities against MCF-8 and HT-29 cell lines with IC50 values of 93.39 ± 3.69 and 71.89 ± 2.94 μM, respectively. Oleanolic acid (17) showed moderate antitumor activity against HT-29 cell lines with an IC50 value of 52.62 ± 1.63 μM. In this study, the discovery of anti-inflammatory, antibacterial and antitumor components from H. cuspidatus could benefit further development and utilization of this plant.

Biosynthetic gene clusters (BGCs) are regions of a genome where genes involved in a biosynthetic pathway are in proximity. The origin and evolution of plant BGCs as well as their role in specialized metabolism remain largely unclear. In this study, we have assembled a chromosome-scale genome of Japanese catnip (Schizonepeta tenuifolia) and discovered a BGC that contains multiple copies of genes involved in four adjacent steps in the biosynthesis of p-menthane monoterpenoids. This BGC has an unprecedented bipartite structure, with mirrored biosynthetic regions separated by 260 kilobases. This bipartite BGC includes identical copies of a gene encoding an old yellow enzyme, a type of flavin-dependent reductase. In vitro assays and virus-induced gene silencing revealed that this gene encodes the missing isopiperitenone reductase. This enzyme evolved from a completely different enzyme family to isopiperitenone reductase from closely related Mentha spp., indicating convergent evolution of this pathway step. Phylogenomic analysis revealed that this bipartite BGC has emerged uniquely in the S. tenuifolia lineage and through insertion of pathway genes into a region rich in monoterpene synthases. The cluster gained its bipartite structure via an inverted duplication. The discovered bipartite BGC for p-menthane biosynthesis in S. tenuifolia has similarities to the recently described duplicated p-menthane biosynthesis gene pairs in the Mentha longifolia genome, providing an example of the convergent evolution of gene order. This work expands our understanding of plant BGCs with respect to both form and evolution, and highlights the power of BGCs for gene discovery in plant biosynthetic pathways.

Systematic phytochemical investigation on the Mongolian medicinal herb Lomatogonium carinthiacum led to the isolation of 12 monoterpenoids including three new secoiridoids (1, 2 and 4) and one new iridoid glycoside (13), one new monoterpenoid alkaloid (3), and three new sesquiterpenoids (14-16). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS) and quantum chemistry computations (including ECD and NMR calculations) were applied to elucidate their structures. Weak immunosuppressive activities were observed for the new isolates via inhibiting T cell proliferation and cytokine IFN-γ secretion in vitro.

This research investigated the evolution of both monoterpenoids and expression profiles of related biosynthesis genes in the MEP pathway in seven different table grape varieties from veraison to maturity stage in two seasons, and the correlation was further evaluated between monoterpenoid accumulation and expression of these genes studied in these varieties. Results showed that linalool, trans-furan linalool oxide, geraniol, and cis-furan linalool oxide were the main compounds in the five Muscat varieties two seasons. \'Zaomeiguixiang\' had the highest contents of geraniol and β-Citronellol. \'Xiangfei\' had the most abundant of linalool and cis-furan linalool oxide, whereas the neutral varieties of \'Moldova\' and \'Christmas Rose\' had the least amount. Monoterpenoid volatiles have been grouped in three evolutionary patterns in the berry development of these varieties. \'Zaomeiguixiang\' and \'Xiangfei\' had distinct different pattern of terpenoids evolution profiles. Pearson\'s correlation analysis showed that in the MEP pathway, the first biosynthesis gene VvDXS3 was significantly correlated to the accumulation of monoterpenoids, and appeared to be an important candidate gene for synthesis of the monoterpenoids.