Dynamic metabolic rewiring enables efficient acetyl-CoA assimilation in Paracoccus denitrificans

Katharina Kremer, Muriel C. F. van Teeseling, Lennart Schada von Borzyskowski, Iria Bernhardsgrütter, Rob J. M. van Spanning, Andrew Gates, Mitja N. P. Remus-Emsermann, Martin Thanbichler, Tobias J. Erb (Lead Author)

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During growth, microorganisms have to balance metabolic flux between energy and biosynthesis. One of the key intermediates in central carbon metabolism is acetyl-CoA, which can be either oxidized in the citric acid cycle or assimilated into biomass through dedicated pathways. Two acetyl-CoA assimilation strategies have been described in bacteria so far, the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). Here, we show that Paracoccus denitrificans uses both strategies for acetyl-CoA assimilation during different growth stages, revealing an unexpected metabolic complexity in the organism’s central carbon metabolism. The EMCP is constitutively expressed on various substrates and leads to high biomass yields on substrates requiring acetyl-CoA assimilation, such as acetate, while the GC is specifically induced on these substrates, enabling fast growth rates. Even though each acetyl-CoA assimilation strategy alone confers a distinct growth advantage, P. denitrificans recruits both to adapt to changing environmental conditions, such as a switch from succinate to acetate. Time-resolved single-cell experiments show that during this switch, expression of the EMCP and GC is highly coordinated, indicating fine-tuned genetic programming. The dynamic metabolic rewiring of acetyl-CoA assimilation is an evolutionary innovation by P. denitrificans that allows this organism to respond in a highly flexible manner to changes in the nature and availability of the carbon source to meet the physiological needs of the cell, representing a new phenomenon in central carbon metabolism.
Original languageEnglish
Pages (from-to)e00805-e00819
Number of pages15
Issue number4
Publication statusPublished - 9 Jul 2019

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