Robustifying Experimental Tracer Design for13C-Metabolic Flux Analysis

Frontiers in Bioengineering and Biotechnology

Martin Beyß¹  Howard Ramirez-Malule²  Victor D. Parra-Peña²  Katharina Nöh³ 

[1] Computational Systems Biotechnology (AVT.CSB), RWTH Aachen University, Aachen, Germany;Escuela de Ingeniería Química, Universidad del Valle, Cali, Colombia;Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, Jülich, Germany;

关键词: 13C-metabolic flux analysis;    experimental design;    isotope labeling experiments;    Streptomyces clavuligerus;    robustification;    information criteria;   

DOI  :  10.3389/fbioe.2021.685323

来源: DOAJ

【 摘 要 】

13C metabolic flux analysis (MFA) has become an indispensable tool to measure metabolic reaction rates (fluxes) in living organisms, having an increasingly diverse range of applications. Here, the choice of the13C labeled tracer composition makes the difference between an information-rich experiment and an experiment with only limited insights. To improve the chances for an informative labeling experiment, optimal experimental design approaches have been devised for13C-MFA, all relying on some a priori knowledge about the actual fluxes. If such prior knowledge is unavailable, e.g., for research organisms and producer strains, existing methods are left with a chicken-and-egg problem. In this work, we present a general computational method, termed robustified experimental design (R-ED), to guide the decision making about suitable tracer choices when prior knowledge about the fluxes is lacking. Instead of focusing on one mixture, optimal for specific flux values, we pursue a sampling based approach and introduce a new design criterion, which characterizes the extent to which mixtures are informative in view of all possible flux values. The R-ED workflow enables the exploration of suitable tracer mixtures and provides full flexibility to trade off information and cost metrics. The potential of the R-ED workflow is showcased by applying the approach to the industrially relevant antibiotic producer Streptomyces clavuligerus, where we suggest informative, yet economic labeling strategies.

【 授权许可】

Unknown