Small but Smart: On the Diverse Role of Small Proteins in the Regulation of Cyanobacterial Metabolism

Abstract

Over the past few decades, bioengineered cyanobacteria have become a major focus of research for the production of energy carriers and high value chemical compounds. Besides improvements in cultivation routines and reactor technology, the integral understanding of the regulation of metabolic fluxes is the key to designing production strains that are able to compete with established industrial processes. In cyanobacteria, many enzymes and metabolic pathways are regulated differently compared to other bacteria. For instance, while glutamine synthetase in proteobacteria is mainly regulated by covalent enzyme modifications, the same enzyme in cyanobacteria is controlled by the interaction with unique small proteins. Other prominent examples, such as the small protein CP12 which controls the Calvin–Benson cycle, indicate that the regulation of enzymes and/or pathways via the attachment of small proteins might be a widespread mechanism in cyanobacteria. Accordingly, this review highlights the diverse role of small proteins in the control of cyanobacterial metabolism, focusing on well-studied examples as well as those most recently described. Moreover, it will discuss their potential to implement metabolic engineering strategies in order to make cyanobacteria more definable for biotechnological applications.

Bottom‐up and top‐down proteomic approaches for the identification, characterization, and quantification of the low molecular weight proteome with focus on short open reading frame‐encoded peptides

“…As an example, numerous highly conserved sORFs have been identified in the human microbiome [103] and their gene products play a potential role in host-microbiome interaction [26]. Furthermore, SEPs are potentially very interesting targets for medicine and biotechnology [104,105].…”

The largely unexplored biology of small proteins in pro‐ and eukaryotes

“…An increasing number of small proteins is also identified in prokaryotes, but a biological function has been assigned for only a few of them [1,26,111,112]. The E.coli proteome data base lists currently about 150 small proteins, but most small proteins are probably not yet identified [26,95].…”

“…An increasing number of small proteins are also identified in prokaryotes, but a biological function has been assigned for only a few of them [1,26,111,112]. The E .…”

“…Detailed analyses indicated the largest effects on genes relevant for phosphate uptake, glycine/serine homeostasis, and nitrate respiration [133]. In cyanobacteria, several small proteins were found to be involved in metabolic regulation [112]. In Synechocystis sp., the small soluble protein AcnSP was shown to modulate aconitase activity and thereby regulating carbon flow into the TCA cycle [134].…”

Cellular and Molecular Strategies in Cyanobacterial Survival—“In Memory of Prof. Dr. Wolfgang Lockau”

“…Springstein et al [ 10 ] reviewed the structural determinants and their role in cyanobacterial morphogenesis. Brandenburg and Klähn [ 11 ] described the role of small regulatory proteins on cyanobacterial metabolism, while Labella et al [ 12 ] focused on the signaling roles of another small regulatory protein PipX in the coordination of nitrogen metabolism. Rachedi et al [ 13 ] provided a mechanistic overview of stress signaling in cyanobacteria.…”