Transcription-translation machinery -- an autocatalytic network coupling all cellular cycles and generating a plethora of growth laws
Recently discovered simple quantitative relations, known as bacterial growth laws, hint on the existence of simple underlying principles at the heart of bacterial growth. In this work, we provide a unifying picture on how these known relations, as well as new relations that we derive, stems from a u...
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Zusammenfassung: | Recently discovered simple quantitative relations, known as bacterial growth
laws, hint on the existence of simple underlying principles at the heart of
bacterial growth. In this work, we provide a unifying picture on how these
known relations, as well as new relations that we derive, stems from a
universal autocatalytic network common to all bacteria, facilitating balanced
exponential growth of individual cells. We show that the core of the cellular
autocatalytic network is the transcription -- translation machinery -- in
itself an autocatalytic network comprising several coupled autocatalytic
cycles, including the ribosome, RNA polymerase, and tRNA charging cycles. We
derive two types of growth laws per autocatalytic cycle, one relating growth
rate to the relative fraction of the catalyst and its catalysis rate, and the
other relating growth rate to all the time scales in the cycle. The structure
of the autocatalytic network generates numerous regimes in state space,
determined by the limiting components, while the number of growth laws can be
much smaller. We also derive a growth law that accounts for the RNA polymerase
autocatalytic cycle, which we use to explain how growth rate depends on the
inducible expression of the rpoB and rpoC genes, which code for the RpoB and C
protein subunits of RNA polymerase, and how the concentration of rifampicin,
which targets RNA polymerase, affects growth rate without changing the
RNA-to-protein ratio. We derive growth laws for tRNA synthesis and charging,
and predict how growth rate depends on temperature, perturbation to ribosome
assembly, and membrane synthesis. |
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DOI: | 10.48550/arxiv.2103.15356 |