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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.

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.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Savoglidis G,da Silveira Dos Santos AX,Riezman I,Angelino P,Riezman H,Hatzimanikatis V

doi

10.1016/j.ymben.2016.04.002

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

46-62

eissn

1096-7176

issn

1096-7184

pii

S1096-7176(16)30010-6

journal_volume

37

pub_type

杂志文章

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