Glycine betaine-mediated transcriptional stimulation links its catabolism and vitamin B12 biosynthesis in Rhizobiaceae
- 1Philipps-University Marburg
Abstract
Glycine betaine (GB) is a trimethylated ammonium compound widely used as a compatible solute, and serves as a carbon, nitrogen, and methyl group source in many members of the Rhizobiaceae. GB is critical for high-level vitamin B2 production, a cofactor synthesized exclusively by microorganisms. Vitamin B2 formation requires multiple methylation steps. In the industrial vitamin B2 production strain Pseudomonas denitrificans, GB has been shown to serve as a methyl group donor through its successive demethylation to glycine and to provide the carbon backbone for the universal porphyrin precursor 5-aminolevulinic acid. Moreover, previous proteomics studies have revealed increased levels of vitamin B2 biosynthetic enzymes in the presence of GB. However, it has remained unclear at what level of gene expression this regulation occurs. Here, using promoter-reporter fusions in the vitamin B2 overproducer Ensifer adhaerens LU2703 and in the low-producer Sinorhizobium meliloti 102F34, we demonstrate that GB activates promoters of both its own catabolic pathway and of major cob operons. Two of these operons encode the complete set of S-adenosylmethionine-dependent methyltransferases required for corrin ring biosynthesis, the foundational, rate-limiting stage in vitamin B12 production. Stimulation of cobE and cobH promoters as well as vitamin B2 production yields followed sigmoidal dose-response curves with saturation in a similar concentration range, suggesting a tight coupling between GB supply and biosynthetic output. Our findings uncover a novel regulatory layer in vitamin B2 biosynthesis and provide promoter-probe set-ups for further exploration of GB-mediated transcriptional control.
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BibTeX
@misc{rauch2026glycine,
title = {{Glycine betaine-mediated transcriptional stimulation links its catabolism and vitamin B12 biosynthesis in Rhizobiaceae}},
author = {C. Rauch and T. Hoffmann and M. Wagner and P. Charoenpanich and J. Gade and F. Ullmann and K. Schneider and H. Schröder and O. Zelder and A. Becker},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751800},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751800v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Glycine betaine-mediated transcriptional stimulation links its catabolism and vitamin B12 biosynthesis in Rhizobiaceae
AU - C. Rauch
AU - T. Hoffmann
AU - M. Wagner
AU - P. Charoenpanich
AU - J. Gade
AU - F. Ullmann
AU - K. Schneider
AU - H. Schröder
AU - O. Zelder
AU - A. Becker
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751800
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751800v1
AB - Glycine betaine (GB) is a trimethylated ammonium compound widely used as a compatible solute, and serves as a carbon, nitrogen, and methyl group source in many members of the Rhizobiaceae. GB is critical for high-level vitamin B2 production, a cofactor synthesized exclusively by microorganisms. Vitamin B2 formation requires multiple methylation steps. In the industrial vitamin B2 production strain Pseudomonas denitrificans, GB has been shown to serve as a methyl group donor through its successive demethylation to glycine and to provide the carbon backbone for the universal porphyrin precursor 5-aminolevulinic acid. Moreover, previous proteomics studies have revealed increased levels of vitamin B2 biosynthetic enzymes in the presence of GB. However, it has remained unclear at what level of gene expression this regulation occurs. Here, using promoter-reporter fusions in the vitamin B2 overproducer Ensifer adhaerens LU2703 and in the low-producer Sinorhizobium meliloti 102F34, we demonstrate that GB activates promoters of both its own catabolic pathway and of major cob operons. Two of these operons encode the complete set of S-adenosylmethionine-dependent methyltransferases required for corrin ring biosynthesis, the foundational, rate-limiting stage in vitamin B12 production. Stimulation of cobE and cobH promoters as well as vitamin B2 production yields followed sigmoidal dose-response curves with saturation in a similar concentration range, suggesting a tight coupling between GB supply and biosynthetic output. Our findings uncover a novel regulatory layer in vitamin B2 biosynthesis and provide promoter-probe set-ups for further exploration of GB-mediated transcriptional control.
ER -