A bioarchitectonic approach to the modular engineering of metabolism

Abstract

Dissociating the complexity of metabolic processes into modules is a shift in focus from the single gene/gene product to functional and evolutionary units spanning the scale of biological organization. When viewing the levels of biological organization through this conceptual lens, modules are found across the continuum: domains within proteins, co-regulated groups of functionally associated genes, operons, metabolic pathways and (sub)cellular compartments. Combining modules as components or subsystems of a larger system typically leads to increased complexity and the emergence of new functions. By virtue of their potential for 'plug and play' into new contexts, modules can be viewed as units of both evolution and engineering. Through consideration of lessons learned from recent efforts to install new metabolic modules into cells and the emerging understanding of the structure, function and assembly of protein-based organelles, bacterial microcompartments, a structural bioengineering approach is described: one that builds from an architectural vocabulary of protein domains. This bioarchitectonic approach to engineering cellular metabolism can be applied to microbial cell factories, used in the programming of members of synthetic microbial communities or used to attain additional levels of metabolic organization in eukaryotic cells for increasing primary productivity and as the foundation of a green economy.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'.

Keywords: bacterial microcompartment; carboxysome; synthetic biology.

Figure 1.

Russian nesting doll (matryoshka) analogy for recursive modularity in cellular metabolism. (a) The conceptual nesting of modules in a cell such as a cyanobacterium which contains, for example, (b) light harvesting modules, multiple pathways and carboxysomes, which are composed of proteins, which are composed of domains, the basic unit of protein fold and function. (c) Enzyme-centric view of pathways in which enzymes are visualized as nodes and the boundaries of the pathway module are demarcated by the flow of metabolites. Rewiring metabolite flow with the addition of new enzymes and the altering of native connections allows new pathway modules to be constructed. (Online version in colour.)

Figure 2.

BMC architectures. (a) Electron micrograph of the cyanobacterium Synechococcus PCC7942 containing numerous carboxysomes (arrows). (b) Empty β carboxysome shells produced in and purified from E. coli, stained with ammonium molybdate and visualized on an electron microscopy grid (see [20] for details). (c) Schematic of the structural elements of bacterial microcompartment shells. Electron micrographs courtesy of Dr Fei Cai. (Online version in colour.)

Figure 3.

BMCs are metabolic modules encoded by genetic modules. Schematics of (a) carboxysome and (b) metabolosome function. (c) Genes for the structural components of the BMC well as gene products providing supporting functions (e.g. transporters for bringing substrates into the cell; cytoskeletal elements for positioning the organelle) are typically encoded together in a genetic module. (Online version in colour.)