A parallel glycolysis provides a selective advantage through rapid growth acceleration

Law, Richard C.; Nurwono, Glenn; Park, Junyoung O.

doi:10.1038/s41589-023-01395-2

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…The provision of reducing power is excessive for this synthetic pathway. ED pathway yields one NADH and one NADPH . The NADPH can support the step of l -aspartate formation, and the cofactor is self-circulated between the steps catalyzed by Asd and DpaAB (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…The ED pathway includes glucose-6-phosphate dehydrogenase ( zwf ), 6-phosphogluconolactonase ( pgl ), 6-phosphogluconate dehydratase ( edd ), and 2-keto-3-deoxygluconate-6-phosphate aldolase ( eda ) . Different from the textbook EMP pathway, the ED pathway needs only four steps to convert glucose to pyruvate, which is accompanied by 1 mol ATP, NADH, and NADPH release . The ED pathway is characterized by its unique NADPH generation, a crucial cofactor for many biosynthetic reactions.…”

Section: Introductionmentioning

confidence: 99%

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Engineering Pseudomonas putida KT2440 for Dipicolinate Production via the Entner–Doudoroff Pathway

Wang,

Zheng,

Xue

et al. 2024

J. Agric. Food Chem.

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Dipicolinic acid (DPA), a cyclic diacid, has garnered significant interest due to its potential applications in antimicrobial agents, antioxidants, chelating reagents, and polymer precursors. However, its natural bioproduction is limited since DPA is only accumulated in Bacillus and Clostridium species during sporulation. Thus, heterologous production by engineered strains is of paramount importance for developing a sustainable biological route for DPA production. Pseudomonas putida KT2440 has emerged as a promising host for the production of various chemicals thanks to its robustness, metabolic versatility, and genetic tractability. The dominant Entner−Doudoroff (ED) pathway for glucose metabolism in this strain offers an ideal route for DPA production due to the advantage of NADPH generation and the naturally balanced flux between glyceraldehyde-3-phosphate and pyruvate, which are both precursors for DPA synthesis. In this study, DPA production via the ED pathway was in silico designed in P. putida KT2440. The systematically engineered strain produced dipicolinate with a titer of 11.72 g/L from glucose in a 5 L fermentor. This approach not only provides a sustainable green route for DPA production but also expands our understanding of the metabolic potential of the ED pathway in P. putida KT2440.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineering Pseudomonas putida KT2440 for Dipicolinate Production via the Entner–Doudoroff Pathway

Wang,

Zheng,

Xue

et al. 2024

J. Agric. Food Chem.

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“…Abnormal proliferation is a hallmark of tumor cells, wherein cells increase the production of biological macromolecules and energy to meet the higher metabolic demands ( 17 , 18 ). Tumor cells, even in the presence of sufficient oxygen for mitochondrial oxidative phosphorylation, tend to metabolize glucose to lactic acid and utilize products such as asparagine, glutamine, and fatty acids to meet their increased metabolic demands rather than induce the more energy-efficient TCA cycle pathway ( 19 – 21 ). Thus, we speculate that if the TCA cycle is blocked, tumor cells can meet the higher metabolic demands through the glycolysis pathway.…”

Section: Discussionmentioning

confidence: 99%

Biomarker Identification and Risk Prediction Model Development for Differentiated Thyroid Carcinoma Lung Metastasis Based on Primary Lesion Proteomics

Peng,

Zhao,

et al. 2024

Clinical Cancer Research

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Purpose: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. Experimental Design: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and immunohistochemistry, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. Results: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS and VDAC2- as potential biomarkers for predicting DTC lung metastasis risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. Conclusions: As a large sample size study in lung metastatic DTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting DTC lung metastasis and establishing personalised treatment strategies.

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Bringing carbon to life via one-carbon metabolism

O’Keeffe,

Garcia,

Chen

et al. 2024

Trends in Biotechnology

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A parallel glycolysis provides a selective advantage through rapid growth acceleration

Cited by 6 publications

References 56 publications

Engineering Pseudomonas putida KT2440 for Dipicolinate Production via the Entner–Doudoroff Pathway

Engineering Pseudomonas putida KT2440 for Dipicolinate Production via the Entner–Doudoroff Pathway

Biomarker Identification and Risk Prediction Model Development for Differentiated Thyroid Carcinoma Lung Metastasis Based on Primary Lesion Proteomics

Bringing carbon to life via one-carbon metabolism

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