Title | Bacillus subtilis PgcA moonlights as a phosphoglucosamine mutase in support of peptidoglycan synthesis. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Patel V, Black KA, Rhee KY, Helmann JD |
Journal | PLoS Genet |
Volume | 15 |
Issue | 10 |
Pagination | e1008434 |
Date Published | 2019 10 |
ISSN | 1553-7404 |
Keywords | Bacillus subtilis, Bacterial Proteins, Gain of Function Mutation, Peptidoglycan, Phosphoglucomutase, Synthetic Lethal Mutations |
Abstract | 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. |
DOI | 10.1371/journal.pgen.1008434 |
Alternate Journal | PLoS Genet |
PubMed ID | 31589605 |
PubMed Central ID | PMC6797236 |
Grant List | R35 GM122461 / GM / NIGMS NIH HHS / United States |