Dynamic Resource Allocation within the Metabolism of Synechococcus Elongatus 7942

Cyanobacteria, also known as blue-green algae, are one of the most important groups of bacteria on earth. They are capable of manufacturing their own nutrients via photosynthesis and are believed to be the ancestors of the chloroplasts we now find in plants. Nowadays, cyanobacteria can be found in almost every terrestrial and aquatic habitat. Recent research pointed out their biotechnological potential in the manufacturing of biofuels, fertilizers, food products, pharmaceuticals etc.

Among cyanobacteria, Synechococcus elongatus was the first one to be reliably transformed by altering its DNA. It is a freshwater cyanobacterium capable of surviving under very poor nutrient conditions. Up to now, the Synechococcus elongatus model is the only developed model for the study of the prokaryotic circadian clock. To this end, we are interested in figuring out when and where resources coming from photosynthesis are allocated during the 24-hour day-night cycle.

Modeling dynamic environmental conditions is crucial for understanding the behavior of photosynthetic organisms, since light availability follows a day-night cycle. For this purpose, we propose a model, the key idea of which is that metabolism is inherently autocatalytic. More precisely, the metabolic network produces the precursors involved in the formation of ribosomes, which in turn help produce the enzymes that in turn catalyze metabolic reactions. Thus, we model processes that happen over two time scales: a fast one - the metabolism, and a slow one - the macromolecule production. We consider the genome-scale metabolic network at steady state, while at the same time we model all metabolic enzymes and ribosome levels dynamically and use them to constrain fluxes through the metabolic network at every point in time. We end up with a dynamic constraint-based model that can be formulated as a linear program.

Our simulations show a clear resource allocation pattern: starting at the beginning of the day, biomass components are produced in order from the most to the least expensive in terms of energy and precursor resources. Components with catalytic activity such as the enzymes and the ribosomes are synthesized first, while structural elements (cell wall, membrane), DNA and RNA are synthesized later in the day. In parallel with this, glycogen is synthesized in order to sustain survival during the night. Most of the metabolic activity happens during day time, which is in good agreement with experimental observations.

We conclude by discussing the issue of why expensive components such as the ribosomes are only used during the day and what would be the energetic impact of also using them during the night. Our method is applicable to other organisms that live in dynamic environments and our results help us understand the principles of resource allocation in photosynthetic organisms.