Multi‐modular engineering for renewable production of isoprene via mevalonate pathway in
            <i>Escherichia coli</i>

Liu, C.‐L.; Dong, Hong‐Gang; Zhan, Jie; Liu, X.; Yang, Yankun

doi:10.1111/jam.14204

Cited by 21 publications

(9 citation statements)

References 32 publications

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“…The IPTG-induced overexpression of genes for (−)-α-bisabolol production can inhibit the essential cellular metabolism due to a deficiency of FPP or accumulation of toxic intermediates (IPP and HMG-CoA) of the heterologous MVA pathway [12]. In contrast, isoprene production increased as the IPTG concentration increased from 0.2 to 1.2 mM [24]. In this study, a small amount of IPTG was effective to increase (−)-α-bisabolol production in the engineered E. coli.…”

Section: Discussionmentioning

confidence: 99%

“…The strengthening of the reducing power for the increased production of terpenoids has been attempted; modulation of glutamate dehydrogenase increased the production of β-carotene and lycopene through the increased supply of NADPH [25][26][27]. The overexpression of GAPDH of C. acetobutylicum also resulted in the improvement of isoprene production [24]. Moreover, the replacement of NAD + -dependent GADPH of E. coli with the NADP + -dependent GAPDH of C. acetobutylicum showed a 2.5-fold increase of lycopene productivity in the engineered E. coli [28].…”

Section: Discussionmentioning

confidence: 99%

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Enhanced (−)-α-Bisabolol Productivity by Efficient Conversion of Mevalonate in Escherichia coli

Kim

Seong

et al. 2019

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(−)-α-Bisabolol, a naturally occurring sesquiterpene alcohol, has been used in pharmaceuticals and cosmetics owing to its beneficial effects on inflammation and skin healing. Previously, we reported the high production of (−)-α-bisabolol by fed-batch fermentation using engineered Escherichia coli (E. coli) expressing the exogenous mevalonate (MVA) pathway genes. The productivity of (−)-α-bisabolol must be improved before industrial application. Here, we report enhancement of initial (−)-α-bisabolol productivity to 3-fold higher than that observed in our previous study. We first harnessed a farnesyl pyrophosphate (FPP)-resistant mevalonate kinase 1 (MvaK1) from an archaeon Methanosarcina mazei (M. mazei) to create a more efficient heterologous MVA pathway that produces (−)-α-bisabolol in the engineered E. coli. The resulting strain produced 1.7-fold higher (−)-α-bisabolol relative to the strain expressing a feedback-inhibitory MvaK1 from Staphylococcus aureus (S. aureus). Next, to efficiently convert accumulated MVA to (−)-α-bisabolol, we additionally overexpressed genes involved in the lower MVA mevalonate pathway in E. coli containing the entire MVA pathway genes. (−)-α-Bisabolol production increased by 1.8-fold with reduction of MVA accumulation, relative to the control strain. Finally, we optimized the fermentation conditions including inducer concentration, aeration and enzymatic cofactor. The strain was able to produce 8.5 g/L of (−)-α-bisabolol with an initial productivity of 0.12 g/L h in the optimal fed-batch fermentation. Thus, the microbial production of (−)-α-bisabolol would be an economically viable bioprocess for its industrial application.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enhanced (−)-α-Bisabolol Productivity by Efficient Conversion of Mevalonate in Escherichia coli

Kim

Seong

et al. 2019

Catalysts

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“…As MVA is a foreign pathway in prokaryotes, all the six genes have to be expressed in the host, namely AtoB (acetoacetyl-CoA thiolase), HMGS (HMG-CoA synthase), HMGR (HMG-CoA reductase), MK (mevalonate kinase), PMK (mevalonate 5-phosphate kinase), and PMD (mevalonate 5-pyrophosphate decarboxylase). These genes can be expressed under the influence of different promoters like trc and T7 and in plasmids with varying copy numbers (Nybo et al 2017 ; Liu et al 2019a , b ). One of the commercially available vectors, ready to use, consisting of all the six genes, was deposited by Peralta-Yahya et al ( 2011 ) in the addgene plasmid repository (Addgene plasmid # 35151).…”

Section: Introductionmentioning

confidence: 99%

Engineering plant family TPS into cyanobacterial host for terpenoids production

Rautela

Kumar

2022

Plant Cell Rep

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Terpenoids are synthesized naturally by plants as secondary metabolites, and are diverse and complex in structure with multiple applications in bioenergy, food, cosmetics, and medicine. This makes the production of terpenoids such as isoprene, β-phellandrene, farnesene, amorphadiene, and squalene valuable, owing to which their industrial demand cannot be fulfilled exclusively by plant sources. They are synthesized via the Methylerythritol phosphate pathway (MEP) and the Mevalonate pathway (MVA), both existing in plants. The advent of genetic engineering and the latest accomplishments in synthetic biology and metabolic engineering allow microbial synthesis of terpenoids. Cyanobacteria manifest to be the promising hosts for this, utilizing sunlight and CO 2 . Cyanobacteria possess MEP pathway to generate precursors for terpenoid synthesis. The terpenoid synthesis can be amplified by overexpressing the MEP pathway and engineering MVA pathway genes. According to the desired terpenoid, terpene synthases unique to the plant kingdom must be incorporated in cyanobacteria. Engineering an organism to be used as a cell factory comes with drawbacks such as hampered cell growth and disturbance in metabolic flux. This review set forth a comparison between MEP and MVA pathways, strategies to overexpress these pathways with their challenges.

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“…The key problems to be solved at present are to screen MK-7 producing strains efficiently and optimize fermentation conditions. Many researchers have used breeding ( Song et al, 2014 ; Xu and Zhang, 2017 ), genetic modification ( Liu et al, 2019 ; Yang et al, 2019 ), and optimized fermentation processes ( Novin et al, 2020 ) to increase the yield of MK-7. With the development of metabolic ( Xu et al, 2017 ; Chen T. et al, 2020 ) and genetic engineering technologies ( Cui et al, 2019 ), related biotechnologies have been extensively studied to regulation MK-7 biosynthesis, while the study of abiotic stress methods to increase MK-7 production limited.…”

Section: Introductionmentioning

confidence: 99%

Effects of Alkali Stress on the Growth and Menaquinone-7 Metabolism of Bacillus subtilis natto

et al. 2022

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Menaquinone-7 (MK-7) is an important vitamin K2, synthesized from the menaquinone parent ring and seven isoprene side chains. Presently, the synthesis of MK-7 stimulated by environmental stress primarily focuses on oxygen stress, while the effect of alkali stress is rarely studied. Therefore, this study researched the effects of alkali stress on the fermentation performance and gene expression of Bacillus subtilis natto. The organism’s growth characteristics, biomass, sporogenesis, MK-7 biosynthesis, and gene expression were analyzed. After a pH 8.5 stress adaptation treatment for 0.5 h and subsequent fermentation at pH 8.5, which promoted the growth of the strain and inhibited the spore formation rate. In addition, biomass was significantly increased (P < 0.05). The conversion rate of glycerol to MK-7 was 1.68 times higher than that of the control group, and the yield of MK-7 increased to 2.10 times. Transcriptomic analysis showed that the MK-7 high-yielding strain had enhanced carbon source utilization, increased glycerol and pyruvate metabolism, enhanced the Embden-Meyerhof pathway (EMP), tricarboxylic acid (TCA) circulation flux, and terpenoid biosynthesis pathway, and promoted the accumulation of acetyl-CoA, the side-chain precursor of isoprene. At the same time, the up-regulation of transketolase increased the metabolic flux of the pentose phosphate (HMP) pathway, which was conducive to the accumulation of D-erythrose 4-phosphate, the precursor of the menadione parent ring. This study’s results contribute to a better understanding of the effects of environmental stress on MK-7 fermentation by Bacillus subtilis natto and the molecular regulatory mechanism of MK-7 biosynthesis.

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Multi‐modular engineering for renewable production of isoprene via mevalonate pathway in Escherichia coli

Cited by 21 publications

References 32 publications

Enhanced (−)-α-Bisabolol Productivity by Efficient Conversion of Mevalonate in Escherichia coli

Enhanced (−)-α-Bisabolol Productivity by Efficient Conversion of Mevalonate in Escherichia coli

Engineering plant family TPS into cyanobacterial host for terpenoids production

Effects of Alkali Stress on the Growth and Menaquinone-7 Metabolism of Bacillus subtilis natto

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