Top-Down, Knowledge-Based Genetic Reduction of Yeast Central Carbon Metabolism

Postma, Erik; Couwenberg, Lucas G.F.; Roosmalen, Roderick N. van; Geelhoed, Jeanine S.; Groot, Philip A. de; Daran‐Lapujade, Pascale

doi:10.1128/mbio.02970-21

Cited by 3 publications

(3 citation statements)

References 182 publications

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“…Therefore, to compensate for its absence, Ctp1 must have a higher transport activity. In accordance with this hypothesis, analysis of the literature shows that Ctp1 has a stricter substrate specificity for tricarboxylic acids, transporting only citrate and isocitrate; malate can be also transported, albeit to a much lesser extent [16,[40][41][42]. Yhm2 seems to be able to transport citrate using a wider variety of counter substrates, including citrate, α-ketoglutarate, oxaloacetate, succinate, and fumarate [17].…”

Section: Discussionmentioning

confidence: 72%

Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae

Assalve,

Lunetti,

Zara

et al. 2024

IJMS

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Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in CTP1 and YHM2 were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of S. cerevisiae.

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Section: Discussionmentioning

confidence: 72%

Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae

Assalve,

Lunetti,

Zara

et al. 2024

IJMS

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“…The CCM consists of key pathways required for the conversion of carbon sources into the 12 building blocks for the synthesis of cellular components and encompasses ca. 150 transport proteins and enzymes ( 28 ). The flow of carbon and electrons via the CCM therefore responds to the carbon source nature and abundance.…”

Section: Resultsmentioning

confidence: 99%

“…Many genes, more particularly those involved in metabolism, have orthologs with similar functions ( 26 ), but often with a poorly understood physiological role. In view of minimal genomes, several studies have explored the requirement for these redundant genes and implemented top–down approaches to reduce genetic redundancy ( 27 , 28 , 29 ). Such minimized genomes have the potential to facilitate the complete redesign and construction of entirely synthetic yeast genomes.…”

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confidence: 99%

Proteome Dynamics During Transition From Exponential to Stationary Phase Under Aerobic and Anaerobic Conditions in Yeast

Ridder¹,

Brandeler²,

Altiner³

et al. 2023

Molecular & Cellular Proteomics

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Promising non-model microbial cell factories obtained by genome reduction

Ravagnan,

Schmid

2024

Front. Bioeng. Biotechnol.

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The development of sustainable processes is the most important basis to realize the shift from the fossil-fuel based industry to bio-based production. Non-model microbes represent a great resource due to their advantageous traits and unique repertoire of bioproducts. However, most of these microbes require modifications to improve their growth and production capacities as well as robustness in terms of genetic stability. For this, genome reduction is a valuable and powerful approach to meet industry requirements and to design highly efficient production strains. Here, we provide an overview of various genome reduction approaches in prokaryotic microorganisms, with a focus on non-model organisms, and highlight the example of a successful genome-reduced model organism chassis. Furthermore, we discuss the advances and challenges of promising non-model microbial chassis.

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Top-Down, Knowledge-Based Genetic Reduction of Yeast Central Carbon Metabolism

Cited by 3 publications

References 182 publications

Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae

Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae

Proteome Dynamics During Transition From Exponential to Stationary Phase Under Aerobic and Anaerobic Conditions in Yeast

Promising non-model microbial cell factories obtained by genome reduction

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