Genome-scale modeling of yeast metabolism: retrospectives and perspectives

FEMS Yeast Research, Journal Year: 2022, Volume and Issue: 22(1)

Published: Jan. 1, 2022

Abstract Yeasts have been widely used for production of bread, beer and wine, as well bioethanol, but they also designed cell factories to produce various chemicals, advanced biofuels recombinant proteins. To systematically understand rationally engineer yeast metabolism, genome-scale metabolic models (GEMs) reconstructed the model Saccharomyces cerevisiae nonconventional yeasts. Here, we review historical development GEMs together with their recent applications, including flux prediction, factory design, culture condition optimization multi-yeast comparative analysis. Furthermore, present an emerging effort, namely integration proteome constraints into GEMs, resulting in improved performance. At last, discuss challenges perspectives on constraints.

Language: Английский

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Development and Perspective of Rhodotorula toruloides as an Efficient Cell Factory

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(4), P. 1802 - 1819

Published: Jan. 23, 2023

Rhodotorula toruloides is receiving significant attention as a novel cell factory because of its high production lipids and carotenoids, fast growth density, well the ability to utilize wide variety substrates. These attractive traits R. make it possible become low-cost producer that can be engineered for various fuels chemicals. However, lack understanding genetic engineering tools impedes metabolic applications. A number research efforts have been devoted filling these gaps. This review focuses on recent developments in tools, advances systems biology improved understandings, emerging strains Finally, future trends barriers developing are also discussed.

Language: Английский

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PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 28, 2023

Abstract Multidimensional measurements using state-of-the-art separations and mass spectrometry provide advantages in untargeted metabolomics analyses for studying biological environmental bio-chemical processes. However, the lack of rapid analytical methods robust algorithms these heterogeneous data has limited its application. Here, we develop evaluate a sensitive high-throughput computational workflow to enable accurate metabolite profiling. Our combines liquid chromatography, ion mobility data-independent acquisition with PeakDecoder, machine learning-based algorithm that learns distinguish true co-elution co-mobility from raw calculates identification error rates. We apply PeakDecoder profiling various engineered strains Aspergillus pseudoterreus, niger, Pseudomonas putida Rhodosporidium toruloides . Results, validated manually against selected reaction monitoring gas-chromatography platforms, show 2683 features could be confidently annotated quantified across 116 microbial sample runs library built 64 standards.

Language: Английский

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Toward rapid and efficient utilization of nonconventional substrates by nonconventional yeast strains

Current Opinion in Biotechnology, Journal Year: 2024, Volume and Issue: 85, P. 103059 - 103059

Published: Jan. 3, 2024

Language: Английский

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Perspective on Lignin Conversion Strategies That Enable Next Generation Biorefineries

ChemSusChem, Journal Year: 2024, Volume and Issue: 17(16)

Published: April 26, 2024

Abstract The valorization of lignin, a currently underutilized component lignocellulosic biomass, has attracted attention to promote stable and circular bioeconomy. Successful approaches including thermochemical, biological, catalytic lignin depolymerization have been demonstrated, enabling opportunities for lignino‐refineries biorefineries. Although significant progress in made, this review describes unexplored chemical biological routes thereby contributes economically environmentally sustainable lignin‐utilizing This also highlights the integration identifies research gaps while recommending future directions scaling processes establish lignino‐chemical industry.

Language: Английский

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Metabolic profiling of two white-rot fungi during 4-hydroxybenzoate conversion reveals biotechnologically relevant biosynthetic pathways

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 13, 2025

White-rot fungi are efficient organisms for the mineralization of lignin and polysaccharides into CO2 H2O. Despite their biotechnological potential, WRF metabolism remains underexplored. Building on recent findings regarding utilization lignin-related aromatic compounds as carbon sources by WRF, we aimed to gain further insights these catabolic processes. For this purpose, Trametes versicolor Gelatoporia subvermispora were incubated in varying conditions – static agitation modes different antioxidant levels during conversion 4-hydroxybenzoic acid (a compound) cellobiose. Their metabolic responses assessed via transcriptomics, proteomics, lipidomics, metabolomics, microscopy analyses. These analyses reveal significant impact cultivation sugar pathways, well lipid composition fungal mycelia. Additionally, study identifies biosynthetic pathways production extracellular fatty acids phenylpropanoids both products with relevance applications provides fate nature. Cultivation white-rot distinct incubation presence a compound induces changes transcriptome, proteome, lipidome, metabolome.

Language: Английский

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Engineering Rhodosporidium toruloides for production of 3-hydroxypropionic acid from lignocellulosic hydrolysate

Metabolic Engineering, Journal Year: 2023, Volume and Issue: 78, P. 72 - 83

Published: May 17, 2023

Language: Английский

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Engineering oleaginous red yeasts as versatile chassis for the production of olechemicals and valuable compounds: Current advances and perspectives

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 76, P. 108432 - 108432

Published: Aug. 18, 2024

Language: Английский

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Metabolic engineering of Rhodotorula toruloides IFO0880 improves C16 and C18 fatty alcohol production from synthetic media

Microbial Cell Factories, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 19, 2022

The oleaginous, carotenogenic yeast Rhodotorula toruloides has been increasingly explored as a platform organism for the production of terpenoids and fatty acid derivatives. Fatty alcohols, derivative widely used in detergents surfactants, can be produced microbially with expression heterologous acyl-CoA reductase. Due to its high lipid production, R. potential alcohol this study several metabolic engineering approaches were investigated improve titer product.Fatty reductase from Marinobacter aqueolei was co-expressed SpCas9 IFO0880 panel gene overexpressions Cas9-mediated deletions increase production. Two overexpression targets (ACL1 ACC1, improving cytosolic acetyl-CoA malonyl-CoA respectively) two deletion (the acyltransferases DGA1 LRO1) resulted significant (1.8 4.4-fold) increases culture tubes. Combinatorial exploration these modifications bioreactor fermentation culminated 3.7 g/L LRO1Δ mutant. As LRO1 not found beneficial other yeasts, lipidomic comparison knockout mutants performed, finding that is primary acyltransferase responsible triacylglyceride toruloides, while disruption simultaneously improved increased diacylglyceride glucose consumption.The reductase-expressing significantly through LRO1, or combined ACC1 ACL1. Disruption surprisingly both creating possible avenue future metabolism yeast.

Language: Английский

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Genome-scale metabolic modeling reveals metabolic trade-offs associated with lipid production in Rhodotorula toruloides

PLoS Computational Biology, Journal Year: 2023, Volume and Issue: 19(4), P. e1011009 - e1011009

Published: April 26, 2023

Rhodotorula toruloides is a non-conventional, oleaginous yeast able to naturally accumulate high amounts of microbial lipids. Constraint-based modeling R . has been mainly focused on the comparison experimentally measured and model predicted growth rates, while intracellular flux patterns have analyzed rather general level. Hence, intrinsic metabolic properties that make lipid synthesis possible are not thoroughly understood. At same time, lack diverse physiological data sets often bottleneck predict accurate fluxes. In this study, we collected detailed physiology growing glucose, xylose, acetate as sole carbon source in chemically defined medium. Regardless source, was divided into two phases from which proteomic lipidomic were collected. Complemental parameters these altogether implemented models. Simulated demonstrated role phosphoketolase generation acetyl-CoA, one main precursors during biosynthesis, ATP citrate lyase confirmed. Metabolic xylose substrate greatly improved by detection chirality D-arabinitol, together with D-ribulose involved an alternative assimilation pathway. Further, pointed trade-offs associated NADPH allocation between nitrogen biosynthetic pathways, linked large-scale differences protein content. This work includes first extensive multi-condition analysis using enzyme-constrained models quantitative proteomics. more precise k cat values should extend application newly developed publicly available for future studies.

Language: Английский

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