Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae

Kirby, James; Dietzel, Kevin; Wichmann, Gale; Chan, Rossana; Antipov, Eugene; Moss, Nathan A.; Baidoo, Edward E. K.; Jackson, Peter; Gaucher, Sara P.; Gottlieb, Shayin S.; LaBarge, Jeremy; Mahatdejkul, Tina; Hawkins, Kristy; Muley, Sheela; Newman, John D.; Liu, Pinghua; Keasling, Jay D.; Zhao, Lishan

doi:10.1016/j.ymben.2016.10.017

Cited by 50 publications

(39 citation statements)

References 46 publications

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“…It is considered the two biosynthesis steps catalyzed by AsmUdpg and Asm14 may be the limiting steps for the AP‐3 biosynthesis in A. pretiosum . To further deepening the mechanism understanding, more studies such as gene knockout, enzyme activity detection, together with analysis of more intracellular metabolites, and pathway module manipulation are required (Kirby et al, ; Rahman, Hasan, Oba, & Shimizu, ).…”

Section: Discussionmentioning

confidence: 99%

Combination of traditional mutation and metabolic engineering to enhance ansamitocin P‐3 production in Actinosynnema pretiosum

Zhang

Qian

et al. 2017

Biotech & Bioengineering

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Ansamitocin P-3 (AP-3) is a maytansinoid with its most compelling antitumor activity, however, the low production titer of AP-3 greatly restricts its wide commercial application. In this work, a combinatorial approach including random mutation and metabolic engineering was conducted to enhance AP-3 biosynthesis in Actinosynnema pretiosum. First, a mutant strain M was isolated by N-methyl-N'-nitro-N-nitrosoguanidine mutation, which could produce AP-3 almost threefold that of wild type (WT) in 48 deep-well plates. Then, by overexpressing key biosynthetic genes asmUdpg and asm13-17 in the M strain, a further 60% increase of AP-3 production in 250-ml shake flasks was achieved in the engineered strain M-asmUdpg:asm13-17 compared to the M strain, and its maximum AP-3 production reached 582.7 mg/L, which is the highest as ever reported. Both the gene transcription levels and intracellular intermediate concentrations in AP-3 biosynthesis pathway were significantly increased in the M and M-asmUdpg:asm13-17 during fermentation compared to the WT. The good fermentation performance of the engineered strain was also confirmed in a lab-scale bioreactor. This work demonstrated that combination of random mutation and metabolic engineering could promote AP-3 biosynthesis and might be helpful for increasing the production of other industrially important secondary metabolites.

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Section: Discussionmentioning

confidence: 99%

Combination of traditional mutation and metabolic engineering to enhance ansamitocin P‐3 production in Actinosynnema pretiosum

Zhang

Qian

et al. 2017

Biotech & Bioengineering

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“…The yeast strain was developed where its MVA pathway was replaced with an MEP pathway. The resulting strain showed a slight growth defect made less biomass compared to the wild type, implying slight incompatibility [67].…”

Section: Terpenoidsmentioning

confidence: 98%

The Smell of Synthetic Biology: Engineering Strategies for Aroma Compound Production in Yeast

2018

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Yeast-especially Saccharomyces cerevisiae-have long been a preferred workhorse for the production of numerous recombinant proteins and other metabolites. S. cerevisiae is a noteworthy aroma compound producer and has also been exploited to produce foreign bioflavour compounds. In the past few years, important strides have been made in unlocking the key elements in the biochemical pathways involved in the production of many aroma compounds. The expression of these biochemical pathways in yeast often involves the manipulation of the host strain to direct the flux towards certain precursors needed for the production of the given aroma compound. This review highlights recent advances in the bioengineering of yeast-including S. cerevisiae-to produce aroma compounds and bioflavours. To capitalise on recent advances in synthetic yeast genomics, this review presents yeast as a significant producer of bioflavours in a fresh context and proposes new directions for combining engineering and biology principles to improve the yield of targeted aroma compounds.

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Section: Terpenoidsmentioning

confidence: 98%

The Smell of Synthetic Biology: Engineering Strategies for Aroma Compound Production in Yeast

Wyk¹,

Kroukamp²,

Pretorius³

2018

Preprint

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Yeast -especially Saccharomyces cerevisiae -have long been a preferred workhorse for the production of numerous recombinant proteins and other metabolites. S. cerevisiae is a noteworthy aroma compound producer, and has also been exploited to produce foreign bioflavour compounds. In the past few years, important strides have been made in unlocking the key elements in the biochemical pathways involved in the production of many aroma compounds. The expression of these biochemical pathways in yeast often involves the manipulation of the host strain to direct the flux towards certain precursors needed for the production of the given aroma compound. This review highlights recent advances in the bioengineering of yeast -including S. cerevisiae -to produce aroma compounds and bioflavours. To capitalise on recent advances in synthetic yeast genomics, this review presents yeast as a significant producer of bioflavours in a fresh context and proposes new directions for combining engineering and biology principles to improve the yield of targeted aroma compounds.

show abstract

Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae

Cited by 50 publications

References 46 publications

Combination of traditional mutation and metabolic engineering to enhance ansamitocin P‐3 production in Actinosynnema pretiosum

Combination of traditional mutation and metabolic engineering to enhance ansamitocin P‐3 production in Actinosynnema pretiosum

The Smell of Synthetic Biology: Engineering Strategies for Aroma Compound Production in Yeast

The Smell of Synthetic Biology: Engineering Strategies for Aroma Compound Production in Yeast

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