Functional organization and regulatory logic of the <i>ped</i> gene cluster in <i>Pseudomonas</i> species

<i>Pseudomonas</i> species display exceptional metabolic versatility that underpins their ecological success and broad relevance for synthetic biology, environmental microbiology, bioremediation, and bioproduction. A central contributor to this versatility is the <i>ped</i> gene cluster, which encodes pyrroloquinoline quinone (PQQ)-dependent dehydrogenases that catalyze the oxidation of a wide range of alcohols and aldehydes. These enzymes support both assimilation and detoxification processes with high catalytic efficiency. This review compiles current knowledge on genetic organization, enzymatic functions, and multi-level regulation of the <i>ped</i> cluster, with a focus on <i>Pseudomonas putida</i> KT2440 and <i>Pseudomonas aeruginosa</i> PAO1. The roles of regulatory components [e.g., the iron (Fe²⁺)-dependent YiaY dehydrogenase and the hybrid PP_2683 histidine kinase] are examined for their capacity to respond to short-chain alcohols through a complex signal transduction network. Additional genetic elements, including <i>pedF</i> and <i>pedG</i>, along with poorly characterized open reading frames (e.g., <i>pedD</i>, <i>PP_2666</i>, and <i>PP_2678</i>), which support enzymatic maturation, electron flow, and modulation of surface-associated behaviors are likewise considered. Comparative analysis across the <i>Pseudomonas</i> genus showed that <i>ped</i>-like clusters are conserved but display substantial differences in gene content and arrangement, suggesting adaptations to specific ecological contexts. We evaluate these elements in detail to define a reference framework for future mechanistic studies. By bringing together functional and regulatory features of the cluster, our article provides a basis for exploiting the Ped system as a modular platform in applied microbiology. This integrated view aims to guide ongoing and future fundamental and applied research on alcohol oxidation in gram-negative bacteria.