Functional organization and regulatory logic of the ped gene cluster in Pseudomonas species

Appl Environ Microbiol. 2026 Mar 18;92(3):e0004626. doi: 10.1128/aem.00046-26. Epub 2026 Feb 18.

Abstract

Pseudomonas 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 ped 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 ped cluster, with a focus on Pseudomonas putida KT2440 and Pseudomonas aeruginosa 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 pedF and pedG, along with poorly characterized open reading frames (e.g., pedD, PP_2666, and PP_2678), which support enzymatic maturation, electron flow, and modulation of surface-associated behaviors are likewise considered. Comparative analysis across the Pseudomonas genus showed that ped-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.

Keywords: PQQ; Pseudomonas putida; alcohol; aldehyde; metabolic engineering; metabolism; one-carbon assimilation; synthetic biology; synthetic metabolism; transcriptional regulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Gene Expression Regulation, Bacterial*
  • Multigene Family*
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / metabolism
  • Pseudomonas putida* / genetics
  • Pseudomonas putida* / metabolism
  • Pseudomonas* / enzymology
  • Pseudomonas* / genetics
  • Pseudomonas* / metabolism

Substances

  • Bacterial Proteins