PhaR

PhaR is a regulatory protein associated with polyhydroxyalkanoate (PHA) metabolism in various bacteria. It is commonly encoded near the phaP and phaCAB gene clusters that govern PHA synthesis and granule formation and is found in several PHA-producing species, including Cupriavidus necator (formerly Ralstonia eutropha), Pseudomonas spp., and Bacillus megaterium.

Function and mechanism

PhaR acts as a transcriptional regulator that helps coordinate the expression of phasin proteins (phaP), which coat and stabilize PHA granules. In the absence of PHA, PhaR binds to promoter regions of phaP and related genes, repressing their transcription. When PHA granules form and accumulate inside the cell, PhaR binds to the granule surfaces rather than to DNA. This sequestration reduces its DNA-binding activity, leading to derepression and increased expression of phaP. The resulting phasin proteins associate with granule surfaces, influencing granule size, number, and stability, and thereby linking PHA accumulation to changes in cellular architecture.

Structure and interactions

PhaR is a relatively small DNA-binding protein that often contains a helix-turn-helix motif suitable for promoter binding. Its activity is governed by the cellular PHA status: low PHA favors DNA binding and repression, while high PHA promotes granule binding and relief of repression. In some species, PhaR may also regulate additional genes beyond phaP, indicating a broader role in PHA-related transcriptional networks.

Significance

Understanding PhaR helps illuminate how bacteria synchronize PHA biosynthesis with granule formation and cell physiology. This knowledge has potential applications in metabolic engineering aimed at increasing bioplastic (PHB) production and optimizing PHA-related traits in industrial strains.