Control of central metabolism's architecture in Escherichia coli: An overview.

Understanding metabolic networks' architecture is central to successfully manipulating metabolic fluxes in microbial cell factories. The transition of central metabolism's architecture from acetogenic to gluconeogenic and from the canonical monocyclic architecture of the Krebs tricarboxylic acids (TCA) cycle to a bicyclic architecture in which the TCA and the dicarboxylic acids (DCA) cycles work in unison, with the glyoxylate bypass fulfilling the anaplerotic function, has been the subject of much debate and remains elusive. In this article, the author sheds light on the intricacies surrounding the transition of central metabolism from one architecture to another and shows that the transition from the monocyclic architecture to the bicyclic architecture is triggered in response to a minimum threshold signal of growth rate (≲0.40h) and is a consequence of competitions, on the one hand. between phosphotransacetylase (PTA) and α-ketoglutarate dehydrogenase (α-KGDH) for their common co-factor, free HS-CoA, and, on the other hand, between catabolic and anaplerotic routs for acetyl phosphate. Further restriction of carbon supply in the bioreactor to the point of starvation forces E. coli to further modify its central metabolism to the PEP-glyoxylate architecture to maintain the redox balance. Interestingly the sudden change from hunger ('famine') to carbon excess ('feast') leads to yet another architecture in which the methylglyoxal pathway figure prominently to maintain the adenylate energy charge. Moreover, the author sheds light on the biochemical implications of each architecture.