Evidence of Isoprenoid Precursor Toxicity in<i>Bacillus subtilis</i>

Sivy, Tami; Fall, Ray; Rosenstiel, Todd N.

doi:10.1271/bbb.110572

Cited by 55 publications

(37 citation statements)

References 27 publications

(34 reference statements)

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“…Hydroxymethylglutaryl CoA (HMG1) reductase catalyzes the rate limiting step of the squalene biosynthesis pathway and its overexpression has been reported to enhance the production of squalene in S. cerevisiae (Farhi M, 2011;Donal KA, 1997;Paddon CJ, 2013). Isopentenyl diphosphate (IDI1) isomerase is a checkpoint that regulates the flux of IPP/DMAPP into the squalene biosynthesis pathway (Martin VJ, 2001;Sivy TL, 2011). Farnesyl diphosphate synthase (ERG20) is at a major intersection of metabolic pathways and catalyzes the biosynthesis of FDP (Farhi M, 2011).…”

Section: Overproduction Of Squalene Simultaneously Reduces the Producmentioning

confidence: 99%

Overproduction of squalene synergistically downregulates ethanol production in Saccharomyces cerevisiae

Rasool

Ahmed

2016

Chemical Engineering Science

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Section: Overproduction Of Squalene Simultaneously Reduces the Producmentioning

confidence: 99%

Overproduction of squalene synergistically downregulates ethanol production in Saccharomyces cerevisiae

Rasool

Ahmed

2016

Chemical Engineering Science

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“…It is produced from one of two pathways: the mevalonate pathway, which is the predominant pathway in yeast and mammals, and the 1-deoxy-D-xylulose-5-phosphate (DXP) pathway, which is functional in most plants and microorganisms [6]. The role of isoprene in bacteria has not been firmly established [8]–[10], but the toxicity of isoprene precursors and the requirement of isoprenoid compounds for normal growth strongly suggest that regulation of this pathway is tightly controlled by the host cell, and must be considered in efforts to alter isoprene production levels in model or non-model organisms [8], [11]. Collectively, we refer to the 11 genes of the DXP pathway and three genes of the mevalonate pathway as the terpenoid genes.…”

Section: Introductionmentioning

confidence: 99%

“…The Idi enzyme (isopentenyl pyrophosphate isomerase), encoded by the fni gene, is responsible for the isomerization reaction between DMAPP and IPP. Evidence from previous studies suggests that DMAPP is converted to isoprene by isoprene synthase (IspS), an enzyme identified in plants but currently unidentified in bacteria [7], [8], [11], [21]. Farnesyl diphosphate synthase (IspA) condenses DMAPP and IPP to produce geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and larger order isoprenoid compounds.…”

Section: Introductionmentioning

confidence: 99%

Coregulation of Terpenoid Pathway Genes and Prediction of Isoprene Production in Bacillus subtilis Using Transcriptomics

et al. 2013

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The isoprenoid pathway converts pyruvate to isoprene and related isoprenoid compounds in plants and some bacteria. Currently, this pathway is of great interest because of the critical role that isoprenoids play in basic cellular processes, as well as the industrial value of metabolites such as isoprene. Although the regulation of several pathway genes has been described, there is a paucity of information regarding system level regulation and control of the pathway. To address these limitations, we examined Bacillus subtilis grown under multiple conditions and determined the relationship between altered isoprene production and gene expression patterns. We found that with respect to the amount of isoprene produced, terpenoid genes fall into two distinct subsets with opposing correlations. The group whose expression levels positively correlated with isoprene production included dxs, which is responsible for the commitment step in the pathway, ispD, and two genes that participate in the mevalonate pathway, yhfS and pksG. The subset of terpenoid genes that inversely correlated with isoprene production included ispH, ispF, hepS, uppS, ispE, and dxr. A genome-wide partial least squares regression model was created to identify other genes or pathways that contribute to isoprene production. These analyses showed that a subset of 213 regulated genes was sufficient to create a predictive model of isoprene production under different conditions and showed correlations at the transcriptional level. We conclude that gene expression levels alone are sufficiently informative about the metabolic state of a cell that produces increased isoprene and can be used to build a model that accurately predicts production of this secondary metabolite across many simulated environmental conditions.

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“…Although lycopene titers obtained with C. glutamicum LYC3-Op1Op2 were comparable to the dxs overexpressing strain LYC3-P tuf dxs (Figure 2 and Table 3), their combination in strain LYC3-MEP was not synergistic and even perturbed growth. This may be explained by accumulation of inhibitory MEP pathway intermediates as shown for B. subtilis (Sivy et al, 2011) and E. coli (Martin et al, 2003; Zou et al, 2013), from an excessive drain of central metabolic intermediates (Kim and Keasling, 2001) and/or from an imbalance between IPP and DMAPP (Kajiwara et al, 1997). In C. glutamicum , improved lycopene production as consequence of overexpression of IPP isomerase gene idi was observed in LYC3-MEP (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Optimization of the IPP Precursor Supply for the Production of Lycopene, Decaprenoxanthin and Astaxanthin by Corynebacterium glutamicum

Heider

Wolf

Hofemeier

et al. 2014

Front. Bioeng. Biotechnol.

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The biotechnologically relevant bacterium Corynebacterium glutamicum, currently used for the million ton-scale production of amino acids for the food and feed industries, is pigmented due to synthesis of the rare cyclic C50 carotenoid decaprenoxanthin and its glucosides. The precursors of carotenoid biosynthesis, isopenthenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate, are synthesized in this organism via the methylerythritol phosphate (MEP) or non-mevalonate pathway. Terminal pathway engineering in recombinant C. glutamicum permitted the production of various non-native C50 and C40 carotenoids. Here, the role of engineering isoprenoid precursor supply for lycopene production by C. glutamicum was characterized. Overexpression of dxs encoding the enzyme that catalyzes the first committed step of the MEP-pathway by chromosomal promoter exchange in a prophage-cured, genome-reduced C. glutamicum strain improved lycopene formation. Similarly, an increased IPP supply was achieved by chromosomal integration of two artificial operons comprising MEP pathway genes under the control of a constitutive promoter. Combined overexpression of dxs and the other six MEP pathways genes in C. glutamicum strain LYC3-MEP was not synergistic with respect to improving lycopene accumulation. Based on C. glutamicum strain LYC3-MEP, astaxanthin could be produced in the milligrams per gram cell dry weight range when the endogenous genes crtE, crtB, and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were coexpressed with the genes for lycopene cyclase and β-carotene hydroxylase from Pantoea ananatis and carotene C(4) oxygenase from Brevundimonas aurantiaca.

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Evidence of Isoprenoid Precursor Toxicity inBacillus subtilis

Cited by 55 publications

References 27 publications

Overproduction of squalene synergistically downregulates ethanol production in Saccharomyces cerevisiae

Overproduction of squalene synergistically downregulates ethanol production in Saccharomyces cerevisiae

Coregulation of Terpenoid Pathway Genes and Prediction of Isoprene Production in Bacillus subtilis Using Transcriptomics

Optimization of the IPP Precursor Supply for the Production of Lycopene, Decaprenoxanthin and Astaxanthin by Corynebacterium glutamicum

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