The potential of the mevalonate pathway for enhanced isoprenoid production

Liao, Pan; Hemmerlin, Andréa; Bach, Thomas J.; Chye, Mee‐Len

doi:10.1016/j.biotechadv.2016.03.005

Cited by 240 publications

(170 citation statements)

References 222 publications

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“…Enhancing the mevalonate pathway by increasing the mRNA level of HMGR has been one strategy to increase the production of specialized metabolites from economically important plants (Liao et al 2016). The enhancement of downstream production Figure 1.…”

Section: Discussionmentioning

confidence: 99%

Evidence that the Arabidopsis thaliana 3-hydroxy-3-methylglutaryl-CoA reductase 1 is phosphorylated at Ser577 in planta

Robertlee

Kobayashi

Tang

et al. 2018

Plant Biotechnology

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3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is an essential enzyme in the mevalonate pathway. In higher plants, mevalonate pathway involves in the production of precursor for isoprenoids biosynthesis, including essential components for cell functions. Previously, we confirmed that the Arabidopsis thaliana HMGR1S (AtHMGR1S) is phosphorylated at S577 by the combination of sucrose non-fermenting related kinase-1 (SnRK1) and geminivirus repinteracting kinase-1 (GRIK1) in vitro. However, even in quantitative phosphoproteomics studies that were directed to find SnRK1 target substrates, AtHMGR1S phosphorylation at S577 has never been detected in planta. In this study, we expressed AtHMGR1S as a C-terminal FLAG-fusion protein in A. thaliana hmg1 mutant to confirm its phosphorylation in planta. Our results provide the first direct evidence that AtHMGR1S is phosphorylated at S577 in planta. Moreover, phosphatase inhibitors treatment to the A. thaliana seedlings induced AtHMGR1S phosphorylation at sites other than S577, suggesting the presence of a novel HMGR regulatory mechanism in planta.

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Section: Discussionmentioning

confidence: 99%

Evidence that the Arabidopsis thaliana 3-hydroxy-3-methylglutaryl-CoA reductase 1 is phosphorylated at Ser577 in planta

Robertlee

Kobayashi

Tang

et al. 2018

Plant Biotechnology

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“…Isoprenoids are a diverse group of natural compounds found in all living organisms, with at least 50,000 different structures already reported (Hemmerlin et al 2012; Liao et al 2016). In plants, these products are derived from the plastididial 2C-methyl-d-erythritol 4-phosphate (MEP) and the cytosolic mevalonate (MVA) pathway.…”

Section: Introductionmentioning

confidence: 99%

Upregulating the mevalonate pathway and repressing sterol synthesis in Saccharomyces cerevisiae enhances the production of triterpenes

Bröker

Müller

Deenen

et al. 2018

Appl Microbiol Biotechnol

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Pentacyclic triterpenes are diverse plant secondary metabolites derived from the mevalonate (MVA) pathway. Many of these molecules are potentially valuable, particularly as pharmaceuticals, and research has focused on their production in simpler and more amenable heterologous systems such as the yeast Saccharomyces cerevisiae. We have developed a new heterologous platform for the production of pentacyclic triterpenes in S. cerevisiae based on a combinatorial engineering strategy involving the overexpression of MVA pathway genes, the knockout of negative regulators, and the suppression of a competing pathway. Accordingly, we overexpressed S. cerevisiae ERG13, encoding 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase, and a truncated and deregulated variant of the rate-limiting enzyme HMG-CoA reductase 1 (tHMGR). In the same engineering step, we deleted the ROX1 gene, encoding a negative regulator of the MVA pathway and sterol biosynthesis, resulting in a push-and-pull strategy to enhance metabolic flux through the system. In a second step, we redirected this enhanced metabolic flux from late sterol biosynthesis to the production of 2,3-oxidosqualene, the direct precursor of pentacyclic triterpenes. In yeast cells transformed with a newly isolated sequence encoding lupeol synthase from the Russian dandelion (Taraxacum koksaghyz), we increased the yield of pentacyclic triterpenes by 127-fold and detected not only high levels of lupeol but also a second valuable pentacyclic triterpene product, β-amyrin.

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“…The phytoalexin biosynthetic requires longer time of incubation than the other antioxidants. This was due to phytoalexin has more complex synthetic process of mevalonate or methylerythritol phosphate pathways (Liao et al, 2016;Dubey et al, 2003;Hunter, 2007). Both processes needed isopentenyldiphosphate and dimethylallyldiphosphate as the important components for phytoalexin synthesis (Okada et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Combining effects of ozone and Xanthomonas oryzae pv. oryzae on antioxidants and phytoalexins in rice (Oryza sativa L.)

Buawat¹,

Hasegawa²,

Umponstira³

2017

Aust J Crop Sci

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Ozone is the most oxidative air pollutant and considered as an abiotic stress which harm to vegetation and crop. Similarly, biological stressor such as plant pathogen could cause severe damage to crops. Combination effects from both stresses will potentially lead to economic loss. Basically, plants will response to both abiotic stress and pathogenic stressor by generate antioxidants and phytoalexins. The concentration of these chemical indicate stress level in plant and also defence system response. This research is aimed to investigate the combination effects of ozone and Xanthomonas oryzae pv. oryzae on antioxidants and phytoalexins in rice (Oryza sativa L. cv. KDML 105). In this study, 45-day-old rice plants were used. Ozone was elevated at concentrations of 100, 200 and 300 ppb in the fumigating chambers for 12 hours. Xanthomonas oryzae pv. oryzae which caused bacterial blight disease in rice was selected as plant pathogen. Combining effects of ozone and Xanthomonas oryzae pv. oryzae were examined using ozone at a concentration of 100 ppb and Xanthomonas oryzae pv. oryzae 1x10 8 cells/ml inoculation. The experimental design was a completely randomized design with 2×2 factorials treatment and three replications required. Temperature, relative humidity and light intensity in fumigating chambers were controlled. The results of the combining effects showed the amount of antioxidants and phytoalexins were higher than those in single treatment. The experimental data indicated that the combining effects will result in more stress in rice. This suggests that, in rice plantation area with experience of ozone episode, pathogenic resistance rice strain should be considered to reduce combining effects.

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The potential of the mevalonate pathway for enhanced isoprenoid production

Cited by 240 publications

References 222 publications

Evidence that the <i>Arabidopsis thaliana</i> 3-hydroxy-3-methylglutaryl-CoA reductase 1 is phosphorylated at Ser577 <i>in planta</i>

Evidence that the <i>Arabidopsis thaliana</i> 3-hydroxy-3-methylglutaryl-CoA reductase 1 is phosphorylated at Ser577 <i>in planta</i>

Upregulating the mevalonate pathway and repressing sterol synthesis in Saccharomyces cerevisiae enhances the production of triterpenes

Combining effects of ozone and Xanthomonas oryzae pv. oryzae on antioxidants and phytoalexins in rice (Oryza sativa L.)

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