Screening Phosphorylation Site Mutations in Yeast Acetyl-CoA Carboxylase Using Malonyl-CoA Sensor to Improve Malonyl-CoA-Derived Product

Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xinhe

doi:10.3389/fmicb.2018.00047

Cited by 36 publications

(43 citation statements)

References 23 publications

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“…Improving synthesis and reducing offtarget consumption of malonyl-CoA are the major areas for overproduction. Acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase (Acc), and improvements in this activity have been achieved by overexpression (Zha et al, 2009;Xu et al, 2011;Yang et al, 2018), ablating posttranslational modification sites (Choi and Da Silva, 2014;Shi et al, 2014;Chen et al, 2018), and improving the availability of its biotin cofactor (Leonard et al, 2007). Acc-independent malonyl-CoA synthesis has also been demonstrated (Leonard et al, 2008), though the pathway requires supplemented malonate.…”

Section: Precursor Supplymentioning

confidence: 99%

Engineering Plant Secondary Metabolism in Microbial Systems

2019

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Secondary metabolites are broadly defined as natural products synthesized by an organism that are not essential to support growth and life. The plant kingdom manufactures over 200,000 distinct chemical compounds, most of which arise from specialized metabolism. While these compounds play important roles in interspecies competition and defense, many plant natural products have been exploited for use as medicines, fragrances, flavors, nutrients, repellants, and colorants. Despite this vast chemical diversity, many secondary metabolites are present at very low concentrations in planta, eliminating crop-based manufacturing as a means of attaining these important products. The structural and stereochemical complexity of specialized metabolites hinders most attempts to access these compounds using chemical synthesis. Although native plants can be engineered to accumulate target pathway metabolites (Zhou et al.

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Section: Precursor Supplymentioning

confidence: 99%

Engineering Plant Secondary Metabolism in Microbial Systems

2019

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“…In order to break through the limitation of low efficiency of this reaction, the Snf1-dependent phosphorylation of ACCase was—at least partially—abolished by introducing two mutations corresponding to Ser1157 and Ser659 of ACC1 ( ACC1 S1157A, S659A ) [33]. An even more efficient catalytic activity was observed when S686A was introduced into the double mutant ACC1 ( ACC1 S1157A, S659A,S686A ) [34]. The resulting higher ratio of malonyl-CoA/acetyl-CoA shifts production towards C18 fatty acids, and the overexpression of either wild-type ACC1 or mutant ACC1 can lead to an improvement in fatty acid production [16,35].…”

Section: Engineering Of Central Carbon Metabolismmentioning

confidence: 99%

Engineering Saccharomyces cerevisiae cells for production of fatty acid-derived biofuels and chemicals

Zhu

Nielsen

et al. 2019

Open Biol.

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The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals, in particular ethanol, a biofuel produced in large quantities. With a need for high-energy-density fuels for jets and heavy trucks, there is, however, much interest in the biobased production of hydrocarbons that can be derived from fatty acids. Fatty acids also serve as precursors to a number of oleochemicals and hence provide interesting platform chemicals. Here, we review the recent strategies applied to metabolic engineering of S. cerevisiae for the production of fatty acid-derived biofuels and for improvement of the titre, rate and yield (TRY). This includes, for instance, redirection of the flux towards fatty acids through engineering of the central carbon metabolism, balancing the redox power and varying the chain length of fatty acids by enzyme engineering. We also discuss the challenges that currently hinder further TRY improvements and the potential solutions in order to meet the requirements for commercial application.

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“…Malonyl-CoA is an important substrate for the production of 3-HP by MCR. It is mainly produced from acetyl-CoA by ACC1, and known as a flux-controlling step ( Tehlivets et al, 2007 ; Chen et al, 2018b ). Therefore, the accumulation of acetyl-CoA in the cytoplasm has a significant impact on the synthesis of 3-HP.…”

Section: Engineering Yeast For Efficient 3-hp Productionmentioning

confidence: 99%

Metabolic Engineering of Yeast for the Production of 3-Hydroxypropionic Acid

Ding

Shi

et al. 2018

Front. Microbiol.

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The beta-hydroxy acid 3-hydroxypropionic acid (3-HP) is an attractive platform compound that can be used as a precursor for many commercially interesting compounds. In order to reduce the dependence on petroleum and follow sustainable development, 3-HP has been produced biologically from glucose or glycerol. It is reported that 3-HP synthesis pathways can be constructed in microbes such as Escherichia coli, Klebsiella pneumoniae and the yeast Saccharomyces cerevisiae. Among these host strains, yeast is prominent because of its strong acid tolerance which can simplify the fermentation process. Currently, the malonyl-CoA reductase pathway and the β-alanine pathway have been successfully constructed in yeast. This review presents the current developments in 3-HP production using yeast as an industrial host. By combining genome-scale engineering tools, malonyl-CoA biosensors and optimization of downstream fermentation, the production of 3-HP in yeast has the potential to reach or even exceed the yield of chemical production in the future.

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Screening Phosphorylation Site Mutations in Yeast Acetyl-CoA Carboxylase Using Malonyl-CoA Sensor to Improve Malonyl-CoA-Derived Product

Cited by 36 publications

References 23 publications

Engineering Plant Secondary Metabolism in Microbial Systems

Engineering Plant Secondary Metabolism in Microbial Systems

Engineering Saccharomyces cerevisiae cells for production of fatty acid-derived biofuels and chemicals

Metabolic Engineering of Yeast for the Production of 3-Hydroxypropionic Acid

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