Affiliation:
1. The Commonwealth Scientific and Industrial Research Organisation, Land & Water Flagship, Acton, Australian Capital Territory, Australia
2. Australian National University, Research School of Chemistry, Acton, Australian Capital Territory, Australia
Abstract
SUMMARY
5-Deazaflavin cofactors enhance the metabolic flexibility of microorganisms by catalyzing a wide range of challenging enzymatic redox reactions. While structurally similar to riboflavin, 5-deazaflavins have distinctive and biologically useful electrochemical and photochemical properties as a result of the substitution of N-5 of the isoalloxazine ring for a carbon. 8-Hydroxy-5-deazaflavin (F
o
) appears to be used for a single function: as a light-harvesting chromophore for DNA photolyases across the three domains of life. In contrast, its oligoglutamyl derivative F
420
is a taxonomically restricted but functionally versatile cofactor that facilitates many low-potential two-electron redox reactions. It serves as an essential catabolic cofactor in methanogenic, sulfate-reducing, and likely methanotrophic archaea. It also transforms a wide range of exogenous substrates and endogenous metabolites in aerobic actinobacteria, for example mycobacteria and streptomycetes. In this review, we discuss the physiological roles of F
420
in microorganisms and the biochemistry of the various oxidoreductases that mediate these roles. Particular focus is placed on the central roles of F
420
in methanogenic archaea in processes such as substrate oxidation, C
1
pathways, respiration, and oxygen detoxification. We also describe how two F
420
-dependent oxidoreductase superfamilies mediate many environmentally and medically important reactions in bacteria, including biosynthesis of tetracycline and pyrrolobenzodiazepine antibiotics by streptomycetes, activation of the prodrugs pretomanid and delamanid by
Mycobacterium tuberculosis
, and degradation of environmental contaminants such as picrate, aflatoxin, and malachite green. The biosynthesis pathways of F
o
and F
420
are also detailed. We conclude by considering opportunities to exploit deazaflavin-dependent processes in tuberculosis treatment, methane mitigation, bioremediation, and industrial biocatalysis.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology,Infectious Diseases
Cited by
150 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献