Abstract
Metabolic flux analysis is a vital tool used to determine the ultimate output of cellular metabolism and thus detect biotechnologically relevant bottlenecks in productivity. 13C-based metabolic flux analysis (13C-MFA) and flux balance analysis (FBA) have many potential applications in biotechnology. However, noteworthy hurdles in fluxomics study are still present. First, several technical difficulties in both 13C-MFA and FBA severely limit the scope of fluxomics findings and the applicability of obtained metabolic information. Second, the complexity of metabolic regulation poses a great challenge for precise prediction and analysis of metabolic networks, as there are gaps between fluxomics results and other omics studies. Third, despite identified metabolic bottlenecks or sources of host stress from product synthesis, it remains difficult to overcome inherent metabolic robustness or to efficiently import and express nonnative pathways. Fourth, product yields often decrease as the number of enzymatic steps increases. Such decrease in yield may not be caused by rate-limiting enzymes, but rather is accumulated through each enzymatic reaction. Fifth, a high-throughput fluxomics tool hasnot been developed for characterizing nonmodel microorganisms and maximizing their application in industrial biotechnology. Refining fluxomics tools and understanding these obstacles will improve our ability to engineer highlyefficient metabolic pathways in microbial hosts.
Highlights
Numerous chemical compounds, ranging from the antimalaria drug artemisinin [1] to the “biofuel” butanol [2, 3], have been produced with the aid of synthetic biology tools
This review paper addresses current developments and challenges in the field of fluxomics, which may guide future study to bridge the gap between systems analysis of cellular metabolism and application in biotechnology
It is desirable to integrate the concepts of systems biology with fluxomics (Figure 2) [48]
Summary
Numerous chemical compounds, ranging from the antimalaria drug artemisinin [1] to the “biofuel” butanol [2, 3], have been produced with the aid of synthetic biology tools. In contrast to traditional omics tools, flux analysis (measurement of metabolite turnover rates) has become instrumental for physiological prediction and enzymatic rate quantification in metabolic networks [4]. This technology allows for the identification of metabolic interactions and the knowledge-based design of cellular functions. The cell-wide quantification of intracellular metabolite turnover rates, was first performed via flux balance analysis (FBA) This method uses the stoichiometry of the metabolic reactions in addition to a series of physical, chemical and biological characteristics (thermodynamics, energy balance, gene regulation, etc.) to constrain the feasible fluxes under a given objective function (e.g., maximal biomass production). This review paper addresses current developments and challenges in the field of fluxomics, which may guide future study to bridge the gap between systems analysis of cellular metabolism and application in biotechnology
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