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Abstract

During growth, microorganisms have to balance metabolic flux between
energy and biosynthesis. One of the key intermediates in central carbon
metabolism is acetyl coenzyme A (acetyl-CoA), which can be either
oxidized in the citric acid cycle or assimilated into biomass through
dedicated pathways. Two acetyl-CoA assimilation strategies in bacteria
have been described 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 high 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.
IMPORTANCE Central carbon metabolism provides organisms with energy and
cellular building blocks during growth and is considered the invariable
"operating system" of the cell. Here, we describe a new phenomenon in
bacterial central carbon metabolism. In contrast to many other bacteria
that employ only one pathway for the conversion of the central
metabolite acetyl-CoA, Paracoccus denitrificans possesses two different
acetyl-CoA assimilation pathways. These two pathways are dynamically
recruited during different stages of growth, which allows P.
denitrificans to achieve both high biomass yield and high growth rates
under changing environmental conditions. Overall, this dynamic rewiring
of central carbon metabolism in P. denitrificans represents a new
strategy compared to those of other organisms employing only one
acetyl-CoA assimilation pathway.