A method for analysis and design of metabolism using metabolomics data and kinetic models: Application on lipidomics using a novel kinetic model of sphingolipid metabolism.
Metab Eng
; 37: 46-62, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27113440
ABSTRACT
We present a model-based method, designated Inverse Metabolic Control Analysis (IMCA), which can be used in conjunction with classical Metabolic Control Analysis for the analysis and design of cellular metabolism. We demonstrate the capabilities of the method by first developing a comprehensively curated kinetic model of sphingolipid biosynthesis in the yeast Saccharomyces cerevisiae. Next we apply IMCA using the model and integrating lipidomics data. The combinatorial complexity of the synthesis of sphingolipid molecules, along with the operational complexity of the participating enzymes of the pathway, presents an excellent case study for testing the capabilities of the IMCA. The exceptional agreement of the predictions of the method with genome-wide data highlights the importance and value of a comprehensive and consistent engineering approach for the development of such methods and models. Based on the analysis, we identified the class of enzymes regulating the distribution of sphingolipids among species and hydroxylation states, with the D-phospholipase SPO14 being one of the most prominent. The method and the applications presented here can be used for a broader, model-based inverse metabolic engineering approach.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfolipasa D
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Saccharomyces cerevisiae
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Esfingolípidos
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Proteínas de Saccharomyces cerevisiae
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Metaboloma
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Análisis de Flujos Metabólicos
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Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Metab Eng
Asunto de la revista:
ENGENHARIA BIOMEDICA
/
METABOLISMO
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suiza