Regulatory mechanism of cysteine-dependent methionine biosynthesis in Bifidobacterium longum: insights into sulfur metabolism in gut microbiota

Abstract

Sulfur, a critical element for bacterial growth, is not directly utilized by bifidobacteria, rendering the sulfur-containing amino acid biosynthesis pathway, particularly for cysteine and methionine, poorly understood. This research identifies six genes involved in this pathway through re-annotation of the Bifidobacterium longum DJO10A genome. These genes play crucial roles in bioconversion processes essential for cysteine utilization, highlighting its significance in sulfur metabolism. Our study uncovers a novel regulatory mechanism of these pathways under varying cysteine concentrations. We demonstrate a dual-pathway mechanism for methionine biosynthesis: one directly utilizing cysteine (trans-sulfurylation pathway) and another utilizing H2S derived from cysteine degradation (direct sulfurylation pathway). This regulatory dual-pathway mechanism is contingent on environmental cysteine levels, with both pathways activated at low cysteine levels, while higher levels predominantly engage the H2S-utilizing pathway. This investigation not only advances our understanding of DJO10A’s metabolic capabilities but also underscores the bacterium’s adaptability through sophisticated regulatory mechanisms for sulfur-containing amino acid biosynthesis. The elucidation of these pathways provides valuable insights into the survival strategies of bifidobacteria in the gut environment, where sulfur sources can vary greatly. Through detailed genomic, transcriptional, and enzymatic analyses, this study significantly contributes to the field of microbiology, offering a foundation for future research on gut microbiota metabolic pathways and their implications for host health.

Keywords

• Bifidobacterium longum
• cysteine auxotroph
• cysteine degradation
• H2S production
• methionine biosynthesis
• sulfur utilization pathway