A functional Wood–Ljungdahl pathway devoid of a formate dehydrogenase in the gut acetogens Blautia wexlerae, Blautia luti and beyond

Abstract

Summary Species of the genus Blautia are typical inhabitants of the human gut and considered as beneficial gut microbes. However, their role in the gut microbiome and their metabolic features are poorly understood. Blautia schinkii was described as an acetogenic bacterium, characterized by a functional Wood–Ljungdahl pathway (WLP) of acetogenesis from H2 + CO2. Here we report that two relatives, Blautia luti and Blautia wexlerae do not grow on H2 + CO2. Inspection of the genome sequence revealed all genes of the WLP except genes encoding a formate dehydrogenase and an electron‐bifurcating hydrogenase. Enzyme assays confirmed this prediction. Accordingly, resting cells neither converted H2 + CO2 nor H2 + HCOOH + CO2 to acetate. Carbon monoxide is an intermediate of the WLP and substrate for many acetogens. Blautia luti and B. wexlerae had an active CO dehydrogenase and resting cells performed acetogenesis from HCOOH + CO2 + CO, demonstrating a functional WLP. Bioinformatic analyses revealed that many Blautia strains as well as other gut acetogens lack formate dehydrogenases and hydrogenases. Thus, the use of formate instead of H2 + CO2 as an interspecies hydrogen and electron carrier seems to be more common in the gut microbiome.

Phylogenetic diversity of the carbon monoxide-utilizing prokaryotes and their divergent carbon monoxide metabolisms in the human gut microbiome

“…The presence of these genes, coupled with the availability of carbohydrates in the human intestinal tract (Martin-Gallausiaux et al 2021), suggests an enhanced provision of substrates for glycolysis, and thereby pyruvate for formate synthesis. Consistent with the above genome-based prediction, previous cultivation experiments have suggested that human gut CO utilizers Blautia luti and B. wexlerae in the order Lachnospirales possess WLP genes but lack Fdh activity (Trischler et al 2022). In addition, although their CO-utilizing ability has not been confirmed, several human gastrointestinal acetogens, including species from Lachnospirales (B. producta, B. schinkii, and Marvinbryantia formatexigens)…”

“…4), and none of the Fdh genes were observed in 79% of the genomes. WLP lacking the Fdh gene is not unprecedented, but some bacterial isolates appear to be capable of CO metabolism with it (Trischler et al . 2022).…”

“…The generated carbonyl and methyl moieties are incorporated into acetyl-CoA along with coenzyme A (CoA) by acetyl-CoA synthase (ACS), which forms a complex with Ni-CODH (CODH/ACS). Acetyl-CoA is then converted into various compounds such as short-chain fatty acids (SCFA), including acetate, by CO utilizers (Miller and Wolin 1996;Trischler et al 2022). In many of these acetogenic CO utilizers, WLP is linked to energy conservation using Rnf complexes and/or energy-converting hydrogenase (Ech), where the oxidation of reduced ferredoxin is coupled with the reduction of NAD + and protons, respectively (Diender et al 2015;Schoelmerich and Müller 2019).…”

“…Although the CO-utilizing abilities of human gut prokaryotes have not yet been fully elucidated, accumulating evidence suggests that CO utilizers are present in the human gut microbiome. Recently, two human gut bacteria, Blautia luti and B. wexlerae, were found to consume CO via the WLP (Trischler et al 2022). Furthermore, several gastrointestinal prokaryotes such as 4 Clostridioides and Marvinbryantia possess genes for WLP (Wolin et al 2003;Yao et al 2023).…”

“…10.5%, 26.7%, and 4.8% of the total human gut microbial genomes derived from the orders Lachnospirales, Veillonelalles, and Oscillospirales, respectively. Within the order Lachnospirales, 38 genera possessed CODH, including Blautia (154/291; 154 Ni-CODH-bearing genomes within 291 of the total genomes of the genus in the human gut microbiome), Fusicatenibacter (67/215), Ruminococcus (29/1,194), Enterocloster (21/56), Anaerobutyricum (12/30), and UMGS1375 (10/11).Of these, Blautia was previously identified as possessing functional WLP(Trischler et al 2022) and was the only taxon to possess three CODHs(HumGut ID:13241, 3275, 5110, 12728, 20698, 11367, and 8982) (…”