Bacillus subtilis PgcA moonlights as a phosphoglucosamine mutase in support of peptidoglycan synthesis

Autoři: Vaidehi Patel aff001;  Katherine A. Black aff002;  Kyu Y. Rhee aff002;  John D. Helmann aff001
Působiště autorů: Department of Microbiology, Cornell University, Ithaca, NY, United States of America aff001;  Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medicine, New York, NY, United States of America aff002
Vyšlo v časopise: Bacillus subtilis PgcA moonlights as a phosphoglucosamine mutase in support of peptidoglycan synthesis. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008434
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008434


Phosphohexomutase superfamily enzymes catalyze the reversible intramolecular transfer of a phosphoryl moiety on hexose sugars. Bacillus subtilis phosphoglucomutase PgcA catalyzes the reversible interconversion of glucose 6-phosphate (Glc-6-P) and glucose 1-phosphate (Glc-1-P), a precursor of UDP-glucose (UDP-Glc). B. subtilis phosphoglucosamine mutase (GlmM) is a member of the same enzyme superfamily that converts glucosamine 6-phosphate (GlcN-6-P) to glucosamine 1-phosphate (GlcN-1-P), a precursor of the amino sugar moiety of peptidoglycan. Here, we present evidence that B. subtilis PgcA possesses activity as a phosphoglucosamine mutase that contributes to peptidoglycan biosynthesis. This activity was made genetically apparent by the synthetic lethality of pgcA with glmR, a positive regulator of amino sugar biosynthesis, which can be specifically suppressed by overproduction of GlmM. A gain-of-function mutation in a substrate binding loop (PgcA G47S) increases this secondary activity and suppresses a glmR mutant. Our results demonstrate that bacterial phosphoglucomutases may possess secondary phosphoglucosamine mutase activity, and that this dual activity may provide some level of functional redundancy for the essential peptidoglycan biosynthesis pathway.

Klíčová slova:

Antibiotics – Biosynthesis – DNA replication – Enzymes – Glucose – Peptidoglycans – Sequence alignment – Bacillus subtilis


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