title: Chemical reactivity drives spatiotemporal organisation of bacterial metabolism.
abstract: In this review, we examine how bacterial metabolism is shaped by chemical constraints acting on the material and dynamic layout of enzymatic networks and beyond. These are moulded not only for optimisation of given metabolic objectives (e.g. synthesis of a particular amino acid or nucleotide) but also for curbing the detrimental reactivity of chemical intermediates. Besides substrate channelling, toxicity is avoided by barriers to free diffusion (i.e. compartments) that separate otherwise incompatible reactions, along with ways for distinguishing damaging vs. harmless molecules. On the other hand, enzymes age and their operating lifetime must be tuned to upstream and downstream reactions. This time dependence of metabolic pathways creates time-linked information, learning and memory. These features suggest that the physical structure of existing biosystems, from operon assemblies to multicellular development may ultimately stem from the need to restrain chemical damage and limit the waste inherent to basic metabolic functions. This provides a new twist of our comprehension of fundamental biological processes in live systems as well as practical take-home lessons for the forward DNA-based engineering of novel biological objects.
authors.affiliation: Systems Biology Program, Centro Nacional de Biotecnología CSIC, Cantoblanco-Madrid, Spain vdlorenzo@cnb.csic.es.
authors.forename: Víctor
authors.initials: V
authors.lastname: de Lorenzo
authors.affiliation: AMAbiotics SAS, Institut du Cerveau et de la Moëlle Épinière, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sekowska
authors.affiliation: AMAbiotics SAS, Institut du Cerveau et de la Moëlle Épinière, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Danchin
mesh_terms: D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*
keywords: TOL plasmid; carboxysomes; metabolic frustration; serine toxicity; synthetic biology