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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products

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Published on: March 12, 2020

Base J: discovery, biosynthesis, and possible functions.

Piet Borst¹, Robert Sabatini

¹Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. p.borst@nki.nl

Annual Review of Microbiology

|August 30, 2008

Summary

This summary is machine-generated.

Base J, a unique DNA modification in kinetoplastids, is found in telomeric repeats and involved in DNA biosynthesis. Its presence and unique structure offer potential for new anti-parasitic drug development.

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Area of Science:

Molecular Biology
Parasitology
Biochemistry

Background:

Base J (beta-d-glucopyranosyloxymethyluracil) is a unique hypermodified DNA base first identified in Trypanosoma brucei.
It is exclusively found in kinetoplastid flagellates and closely related unicellular organisms, but not in other protozoa or metazoa.
Base J is consistently located in telomeric repeats across analyzed species.

Purpose of the Study:

To review the identification, genomic localization, and biosynthesis of Base J in kinetoplastids.
To explore the potential biological functions of Base J.
To assess Base J as a potential therapeutic target for kinetoplastid-caused diseases.

Main Methods:

Literature review of studies on Base J identification and characterization.
Analysis of genomic localization data across various kinetoplastid species.
Discussion of enzymatic pathways involved in Base J synthesis.

Main Results:

Base J is a hypermodified DNA base present in the nuclear DNA of kinetoplastids, primarily in telomeric repeats.
Its biosynthesis involves a two-step process: thymidine conversion to hydroxymethyldeoxyuridine (HOMedU), followed by glycosylation.
Genomic localization of Base J varies, with most found in telomeres in Leishmania, but also in other repetitive sequences in T. brucei and T. cruzi, and outside telomeres in Euglena.

Conclusions:

Base J is a distinctive DNA component in kinetoplastids with a conserved presence in telomeric regions.
The unique biosynthesis pathway and specific localization suggest important biological roles.
Base J represents a promising target for developing novel chemotherapies against kinetoplastid infections.