Can NMR solve some significant challenges in metabolomics?

Abstract

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact biospecimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory.

Recent Advances in NMR-Based Metabolomics

“…25 A selected class of metabolites can be reacted with chemoselective tags containing a stable isotope such as 13 C, 15 N, or 31 P, which is favorable to NMR detection with enhanced resolution and sensitivity. Recently, the chemoselective derivatization approach was extended to the identification of metabolites with free keto and aldehyde groups.…”

“…A recent article presents some perspective on the ability of NMR to alleviate this and other bottlenecks in metabolomics. 25 The emerging trends in NMR-based metabolomics in the areas of improved metabolite detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites are discussed in some detail, highlighting both the opportunities and challenges. The complexity of biological specimens demands new approaches for unknown identification.…”

Metabolomics, a Powerful Tool for Agricultural Research

“…NMR guarantees stable sensitivity as samples and instruments are devoid of contact during detection, eliminating the concerns of gradual contamination by residual metabolites that may compromise sensitivity in MS analyses. In addition, NMR provides the same signal sensitivity for all metabolites regardless of the complexities of the biological matrix, and is independent of the chemical properties of the metabolites [25]. NMR is a powerful technique for the analysis of metabolite structures, as it can differentiate compounds with identical masses and two-dimensional structures that differ only in spatial configuration [26,27].…”

“…A major drawback of NMR technique, however, lies in its sensitivity [24,25,28], which restrains its application to the detection of metabolites of low-abundance in plants. In addition, as molecular weight increases, for example, for lipids comprising long fatty chains, its identification capacity is weakened rapidly due to more complex and overlapping signals from the extended hydrocarbon chains in such compounds.…”

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine

“…LC-MS is a very sensitive technique, and it has the advantage of not requiring chemical derivatization of compounds; however, it has poor resolution. Also, the high capacity of CE-MS to separate compounds allows its use as a platform for multiplexing samples (Johanningsmeier et al, 2014; Nagana Gowda and Raftery, 2015). …”