Metabolomics: Peripheral or central to synthetic biology?

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Carolus Reinecke, Gerhard Koekemoer and Marli Dercksen

North-West University, South Africa

Conceptually, clinical chemistry progressively transformed from mainly an analytical science, through inputs from information technology and now through the emerging synthetic biology with its strong engineering character. Metabolomics is a biotechnology that may contribute to these developments. Its relationship with synthetic biology is still in its infancy (Oldham et al. 2012, PLoS ONE, 7 (e34368), 1-15), but it is clearly a growing relationship (Ellis and Goodacre 2012, Current Opinion in Biotechnology, 23, 22-28). Here we present our views on the implications for synthetic biology of knowledge that we generated through metabolomics investigations of inherited metabolic diseases (Reinecke et al. Metabolomics, 8, 264-283) and their treatment through interventions (Dercksen et al. Metabolomics – In press DOI 10.1007/s11306-013-0501-5). Our investigation included a new bio-statistical application of concurrent class analysis which disclosed different metabolic patterns encapsulated within the data sets that would not have been revealed by using only the conventional modes of multivariate analysis. Moreover, the investigation was done on patients carrying the same homozygous c.367 G>A nucleotide change in exon 4 of the gene for isovaleryl-CoA dehydrogenase. These individuals, however, showed clear phenotype diversity, including diversity in response to treatment. The detection of informative metabolites of even very low concentrations in the patient group highlights the potential advantage of the holistic mode of analysis of diseases through a metabolomics approach. This knowledge is not peripheral to potential applications of synthetic biology in health and disease. A prerequisite of any design process envisaged to produce beneficial artifacts aimed at improved personalized medicine should conspicuously take the complex genotype-phenotype relation into account, as indicated by this illustrative investigation, informing also on the societal and ethical debate affecting the application of synthetic biology and related bio-technologies (Jochemsen and Reinecke, 2011, In: From technological transfer to intercultural development, ISBN 978-1-920383-28-2, p. 51-65).