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Molecular and Cellular Microbiology (MCM) | Microbial Genetics, Physiology and Metabolism
Microbiol. Biotechnol. Lett. 2021; 49(4): 478-484
School of Life Science, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea
Correspondence to :
Juhyun Kim, firstname.lastname@example.org
Cellular resources including transcriptional and translational machineries in bacteria are limited, yet microorganisms depend upon them to maximize cellular fitness. Bacteria have evolved strategies for using resources economically. Regulatory networks for the gene expression system enable the cell to synthesize proteins only when necessary. At the same time, regulatory interactions enable the cell to limit losses when the system cannot make a cellular profit due to fake substrates. Also, the architecture of the gene expression flow can be advantageous for clustering functionally related products, thus resulting in effective interactions among molecules. In addition, cellular systems modulate the investment of proteomes, depending upon nutrient qualities, and fast-growing cells spend more resources on the synthesis of ribosomes, whereas nonribosomal proteins are synthesized in nutrient-limited conditions. A deeper understanding of cellular mechanisms underlying the optimal allocation of cellular resources can be used for biotechnological purposes, such as designing complex genetic circuits and constructing microbial cell factories
Keywords: Resource allocation, growth law, regulatory network, cellular economy
When given a choice between identical goods, no one would purchase costlier commodities. Instead, a person would select the cheapest option, as it would provide us with the best value. This choice is a result of economic behavior that manages scarce resources optimally to maximize desire. In addition, such a rational choice allows us to survive and prosper in a competitive environment.
By the same token, bacteria are capable of adapting to diverse environmental niches by optimizing the allocation of limited cellular resources. In nutrient-rich conditions, microorganisms can increase ribosome content, thus resulting in a higher ATP budget with larger gene expression machineries [1−3]. Eventually, this contributes to maximizing cellular fitness. On the other hand, when cells grow in a nutrient-poor medium, a minimum fraction of cellular resources is allocated to maintain a certain level of growth [4, 5]. This linear relationship between the mass fraction of cellular components and the growth rate indicates that bacteria control the use of their cellular assets, which represent energy currency and building blocks . In other words, a bacterial cell can be considered as a closed economic system . Because of the cellular complexity, it is not straightforward to engineer a biological system with synthetic circuits
Biological systems are composed of dynamic networks that determine the gene expression level depending upon both intracellular and extracellular cues [7−9]. Owing to the regulatory network of the gene expression system, living organisms can synthesize only necessary proteins in given conditions. This allows cells to reduce the protein synthesis cost, which is defined as a reduced growth rate due to limited cellular resources with a
With respect to the gene expression system in a bacterial cell, this review addresses current understanding of cellular strategies for managing scarce resources and for optimizing cellular fitness with respect to the gene expression system. Moreover, the description below provides a guide for manipulating resource allocation for diverse biotechnological purposes.
Many functionally related genes are grouped into operons and are coregulated by particular cues in bacteria. As a result of regulation, a single polycistronic mRNA molecule can be transcribed from cluster genes, which are governed by the same expression system. Due to spatial organization of genes and an efficient mechanism for activating/inhibiting grouped genes, cells can achieve economic allocation of cellular resources. In turn, synthesis of the right enzymes at the right time as the investment step is a way to produce more cellular assets, which appear as energy sources and building blocks (Fig. 1A).
The best examples of these strategies are well addressed in
However, such an expression system achieves no return on investment. This failure occurs when non-productive substrates enhance the switch of metabolic systems. Although bacterial transcriptional factors are robust and evolvable, they sense fake chemicals that do not provide any returns. This aspect is observed in the TOL system, which is encoded by the plasmid pWW0 of
Spatial organization of macromolecules can provide an extra layer for optimizing the use of resources, because the physical arrangements of clustering of functionally related molecules in a system generate efficient interactions . For instance, the expression flow of the
Interestingly, many proteins localize at their functional cellular domains through RNA targeting. It was reported that
Gene expression machineries including RNA polymerase and ribosomes are not abundant in bacterial cells, and therefore, the expression of a particular gene can affect the activity of another seemingly unconnected gene [42−44]. This is mainly caused by the limited number of ribosomes and growing number of observations that have shown that the accumulation of one gene product led to a decrease in the expression of the other gene in a circuit following a linear relationship [42−48]. This tradeoff also appears with cellular proteomes. In
The key source of the translational machineries is
Remarkably, the translation elongation rate also contributes to the cellular economy. It was recently reported that glycerol-grown cells exhibited
The transfer of genetic information plays a fundamental role in living organisms, and this is mainly achieved by the gene expression system. Maintaining and operating the system economically is crucial for maximizing cellular fitness. In this respect, bacteria possess several strategies for the optimal allocation of cellular DNA organization, and operon structures with regulatory networks enable the cell to reduce its operating costs for synthesizing proteins; thus, they can achieve either higher production or minimized losses in response to energy producing substrates or fake substrates, respectively. In addition, spatial distribution of cellular components into functional domains contributes to efficient and effective interactions among functionally related molecules. Moreover, the cell is capable of modulating the partition of cellular proteomes, depending upon nutrient quality; therefore the cellular budget is used economically. These findings guide better understanding of such strategies with respect to the gene expression system, which enables us to design rational DNA circuits, pathways, and a cellular chassis that support the maximum expression of desired biologics. Furthermore, manipulation of the allocation resource is crucial for engineering living systems for advanced bacterial programming.
The authors have no financial conflicts of interest to declare.