Microbial Phenazines: Biosynthesis, Structural Diversity, Evolution, Regulation, and Biological Significance

Authors: Mavrodi, Dmitri; BLANKENFELDT, WULF - Helmholtz Centre; Weller, David; Thomashow, Linda; MAVRODI, OLGA - Washington State University

Submitted to: Microbiology and Molecular Biology Reviews
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/8/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: Phenazines are a diverse group of heterocyclic nitrogen-containing and redox-active compounds that are produced by a wide range of bacteria. They are one of the most important group of metabolites produced by bacteria in nature. Many phenazines have antimicrobial activity against fungi, bacteria and viruses and have pharmacological potential due to their antitumor properties. Phenazines have been used to control plant and animal diseases. Phenazines play a wide range of roles in nature and contribute to the ecology, survival, plant and animal interactions, pathogenicity and biocontrol activity of the bacteria that produce them. This paper addresses gaps in our knowledge about phenazines by providing an updated census of microbial taxa capable of producing phenazines and focuses on the diversity and evolution of phenazine biosynthesis. It also presents new data and results, and summarizes our current understanding of the multifaceted contribution of these fascinating secondary metabolites to bacterial physiology and ecology functions.

Technical Abstract: The research paper provides a comprehensive, up-to-date overview of microbial phenazines, highlighting the diversity of metabolites and the role of horizontal gene transfer events in the evolution of biosynthesis pathways across different clades of Gram-negative and Gram-positive bacteria. The review also discusses the regulatory mechanisms controlling phenazine production, particularly in fluorescent pseudomonads, where quorum sensing and two-component systems modulate biosynthesis in response to environmental cues such as nutrient availability and stress factors. Furthermore, the role of phenazines in bacterial physiology is emphasized, noting their mode of action and function as redox-active compounds that facilitate electron transfer and enhance survival under anaerobic conditions. Finally, we explore the ecological implications of phenazines by covering their role in microbial interactions, toxin effects, and influence on microbial community dynamics in various environments, particularly in soil and plant-associated habitats. The findings underscore the importance of phenazines in both ecological interactions and potential applications in agriculture and medicine, advocating for further exploration of their biosynthetic pathways and ecological functions.