Abstract
AbstractThe yeast Saccharomyces cerevisiae is an attractive industrial microorganism for the production of foods and beverages as well as for various bulk and fine chemicals, such as biofuels or fragrances. Building blocks for these biosyntheses are intermediates of yeast central carbon metabolism (CCM), whose intracellular availability depends on balanced single reactions that form metabolic fluxes. Therefore, efficient product biosynthesis is influenced by the distribution of these fluxes. We recently demonstrated great variations in CCM fluxes between yeast strains of different origins. However, we have limited understanding of flux modulation and the genetic basis of flux variations. In this study, we investigated the potential of quantitative trait locus (QTL) mapping to elucidate genetic variations responsible for differences in metabolic flux distributions (fQTL). Intracellular metabolic fluxes were estimated by constraint-based modelling and used as quantitative phenotypes, and differences in fluxes were linked to genomic variations. Using this approach, we detected four fQTLs that influence metabolic pathways. The molecular dissection of these QTLs revealed two allelic gene variants, PDB1 and VID30, contributing to flux distribution. The elucidation of genetic determinants influencing metabolic fluxes, as reported here for the first time, creates new opportunities for the development of strains with optimized metabolite profiles for various applications.
Publisher
Springer Science and Business Media LLC
Reference83 articles.
1. Cavalieri, D., McGovern, P. E., Hartl, D. L., Mortimer, R. & Polsinelli, M. Evidence for S. cerevisiae fermentation in ancient wine. J. Mol. Evol. 57, S226–S232 (2003).
2. Nielsen, J., Larsson, C., van Maris, A. & Pronk, J. T. Metabolic engineering of yeast for production of fuels and chemicals. Curr. Opin. Biotechnol. 24, 398–404 (2013).
3. Mattanovich, D., Gasser, B., Egermeier, M., Marx, H. & Sauer, M. Industrial Microorganisms: Saccharomyces cerevisiae and other Yeasts. Ind. Biotechnol. Microorg. 2, 673–686 (2017).
4. Neidhardt, F. C., Ingraham, J. L. & Schaechter, M. Physiology of the bacterial cell: a molecular approach. 20, (Sinauer Associates Sunderland, MA, 1990).
5. Ma, H.-W. & Zeng, A.-P. The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 19, 1423–1430 (2003).
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献