T1 - Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth

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Biosynthesis of Cholesterol, Steroids, and Isoprenoids

The structures of C80, C81 and C82isoprenoid tetraacids have been finely described ().

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Five Questions about Non-Mevalonate Isoprenoid Biosynthesis

To clarify stress response gene expression associated with high carotenoid production, we used Enterococcus gilvus isolated from cow’s raw milk which is able to produce high amount of carotenoid. As stress treatment, E. gilvus cells, which were incubated anaerobically, were shaken (aerobic condition). On the other hand, anaerobic incubation of E. gilvus is continued as non-stress treatment (anaerobic condition). To investigate stress response genes associated with carotenoid production, the gene expression levels of the mevalonate biosynthesis pathway (hmgs and hmgr), the isoprene biosynthesis pathway (mvk, pmvk, mpd, ipi and ispA) and the carotenoid biosynthesis pathway (crtM and crtN) were examined using real-time PCR. Compared with anaerobic condition, all genes excluding hmgs were upregulated in aerobic condition (Fig. 1.). We could show that upregulation of isoprenoid biosynthesis genes occurred under aerobic condition and led to enhancement of carotenoid production. To enhance stress-tolerant LAB, mutagenesis in the isoprenoid biosynthesis pathway is considered to be a useful. Furthermore, LAB with high levels of carotenoid production may contribute to supply fermented products with carotenoid considered as antioxidant.

Isoprenoid biosynthesis via the mevalonate pathway.12 …

Fig. 1. The dynamics of isoprenoid biosynthesis pathway and cell pigment under aerobic condition in Enterococcus gilvus. Gene names in bold are upregulated under aerobic condition (red arrows). The yellow pigment level of cell pellets in aerobic conditions (right) was higher in anaerobic (left).

Isoprenoid Biosynthesis in Synechocystis sp

The MEP pathway as defined for E

Microbial production can be advantageous over the extraction of phytoterpenoids from natural plant sources, but it remains challenging to rationally and rapidly access efficient pathway variants. Previous engineering attempts mainly focused on the mevalonic acid (MVA) or methyl--erythritol phosphate (MEP) pathways responsible for the generation of precursors for terpenoids biosynthesis, and potential interactions between diterpenoids synthases were unexplored. Miltiradiene, the product of the stepwise conversion of (,,)-geranylgeranyl diphosphate (GGPP) catalyzed by diterpene synthases SmCPS and SmKSL, has recently been identified as the precursor to tanshionones, a group of abietane-type norditerpenoids rich in the Chinese medicinal herb . Here, we present the modular pathway engineering (MOPE) strategy and its application for rapid assembling synthetic miltiradiene pathways in the yeast . We predicted and analyzed the molecular interactions between SmCPS and SmKSL, and engineered their active sites into close proximity for enhanced metabolic flux channeling to miltiradiene biosynthesis by constructing protein fusions. We show that the fusion of SmCPS and SmKSL, as well as the fusion of BTS1 (GGPP synthase) and ERG20 (farnesyl diphosphate synthase), led to significantly improved miltiradiene production and reduced byproduct accumulation. The MOPE strategy facilitated a comprehensive evaluation of pathway variants involving multiple genes, and, as a result, our best pathway with the diploid strain YJ2X reached miltiradiene titer of 365 mg/L in a 15-L bioreactor culture. These results suggest that terpenoids synthases and the precursor supplying enzymes should be engineered systematically to enable an efficient microbial production of phytoterpenoids.

Fosmidomycin and its analogue FR-900098 are potent inhibitors of 1-deoxy--xylulose 5-phosphate reducto-isomerase (DXR), the second enzyme of the MEP pathway for the biosynthesis of isoprenoids. This paper describes the synthesis of analogues of the two reverse phosphonohydroxamic acids 3 and 4, in which the length of the carbon spacer is modified, the -methyl group of 3 is replaced by an ethyl group, and the phosphate group is replaced by potential isosteric moieties, i.e., sulfonate or carboxylate functionalities. The potential of the synthesized analogues to inhibit the DXR was evaluated.

Molecules | Special Issue : Isoprenoid Biosynthesis

coli is not the major route for isoprenoid biosynthesis in Synechocystis under ..

Lactic acid bacteria (LAB) is industrial important bacteria because LAB are used in fermented foods and probiotics. The clarification of the stress tolerance mechanism of LAB is beneficial for probiotic and molecular breeding to equip LAB with stress tolerance. The increased stress tolerance of LAB can lead to efficient productivity of metabolites and high survivability in the gut environment. The objective of this study is the clarification of stress response mechanism including carotenoid in LAB considered as novel stress tolerance mechanism in LAB. In general, carotenoid plays role in photo-biosynthesis and antioxidant in plants and microorganisms. A part of LAB belonging to Enterococcus and Lactobacillus have yellow pigment, and the yellow pigment is carotenoid named as diaponeurosporene which can enhance oxidative stress tolerance as well as bile acid and lysozyme. However, the gene expression response of carotenoid and its precursor biosynthesis pathways, such as the isoprene biosynthesis pathway via mevalonate, to oxidative stress is not understood in detail.

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  • parallels to isoprenoid biosynthesis from primary ..

    isoprenoid biosynthetic pathway in ..

  • Isoprenoid biosynthesis in bacterial pathogens.

    The only link between tRNA biosynthesis and the isoprenoid pathway is the Mod5p-catalyzed reaction of tRNA ..

  • Isoprenoid Biosynthesis via the Methylerythritol …

    14/12/2017 · Isoprenoid biosynthesis is essential for cell survival

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