Unravelling Formaldehyde Metabolism in Bacteria: Road towards Synthetic Methylotrophy

Klein, Vivien Jessica; Irla, Marta; López, Marina Gil; Brautaset, Trygve; Brito, Luciana Fernandes de

doi:10.3390/microorganisms10020220

Cited by 15 publications

(13 citation statements)

References 177 publications

(398 reference statements)

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“…Thus, reduced growth of the ADH knockout strain could be explained by the potential accumulation of formaldehyde. There are numerous metabolic pathways in which formaldehyde can be detoxified (Yurimoto et al 2005 ; Klein et al 2022 ). However, in the thiol-dependent formaldehyde detoxification, a zinc-dependent ADH and an esterase perform the key reactions (Sanghani et al 2000 ; Gonzalez et al 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Unique alcohol dehydrogenases involved in algal sugar utilization by marine bacteria

Brott

Nam

Thomas

et al. 2023

Appl Microbiol Biotechnol

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Marine algae produce complex polysaccharides, which can be degraded by marine heterotrophic bacteria utilizing carbohydrate-active enzymes. The red algal polysaccharide porphyran contains the methoxy sugar 6-O-methyl-d-galactose (G6Me). In the degradation of porphyran, oxidative demethylation of this monosaccharide towards d-galactose and formaldehyde occurs, which is catalyzed by a cytochrome P450 monooxygenase and its redox partners. In direct proximity to the genes encoding for the key enzymes of this oxidative demethylation, genes encoding for zinc-dependent alcohol dehydrogenases (ADHs) were identified, which seem to be conserved in porphyran utilizing marine Flavobacteriia. Considering the fact that dehydrogenases could play an auxiliary role in carbohydrate degradation, we aimed to elucidate the physiological role of these marine ADHs. Although our results reveal that the ADHs are not involved in formaldehyde detoxification, a knockout of the ADH gene causes a dramatic growth defect of Zobellia galactanivorans with G6Me as a substrate. This indicates that the ADH is required for G6Me utilization. Complete biochemical characterizations of the ADHs from Formosa agariphila KMM 3901T (FoADH) and Z. galactanivorans DsijT (ZoADH) were performed, and the substrate screening revealed that these enzymes preferentially convert aromatic aldehydes. Additionally, we elucidated the crystal structures of FoADH and ZoADH in complex with NAD+ and showed that the strict substrate specificity of these new auxiliary enzymes is based on a narrow active site. Key points • Knockout of the ADH-encoding gene revealed its role in 6-O-methyl-D-galactose utilization, suggesting a new auxiliary activity in marine carbohydrate degradation. • Complete enzyme characterization indicated no function in a subsequent reaction of the oxidative demethylation, such as formaldehyde detoxification. • These marine ADHs preferentially convert aromatic compounds, and their strict substrate specificity is based on a narrow active site.

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Section: Discussionmentioning

confidence: 99%

Unique alcohol dehydrogenases involved in algal sugar utilization by marine bacteria

Brott

Nam

Thomas

et al. 2023

Appl Microbiol Biotechnol

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“…The GDP-D-glycero-α-D-manno-heptose biosynthesis in SG_N remained unclear while heptose-containing bacterial natural products are considered sources of novel bacterial drug [40]. In patients with H. pyloric and AG infections, formaldehyde assimilation I (serine pathway) was the only pathway that showed a signi cant decrease [41]. Formaldehyde assimilation is a pathway for bacterial detoxi cation that plays important roles in methylotrophs, and depletion of this pathway may lead to a decrease in Bacillus [42].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, our ndings indicate that the development of AG_N is associated with lower vitamin B12 levels, whereas the pathogenic mechanism of AG_P is mainly related to gallate and amino acid degradation and heme biosynthesis. However, the roles of these signi cantly altered functional pathways in the development and occurrence of AG require further study [41].…”

Section: Discussionmentioning

confidence: 99%

A Meta-analysis Reveals Gastric Microbes Associated with Atrophic Gastritis

Gao

Yin

Ren

et al. 2023

Preprint

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Previous studies have associated microbial alterations with gastritis; however, problems regarding the reproducibility of biomarkers in cohorts remain poorly resolved. Patients from different regions provided excellent information, that was conducive to the exploration of the gastric microbes associated with gastric inflammation. We performed a meta-analysis of seven reliable datasets, consisting of a total of 367 fecal 16s rRNA including atrophic gastritis (AG) (174 patients) and superficial gastritis (SG) (170 patients) after quality control and discarding samples of gastric fluid, since the microbial diversity between gastric fluid and antrum was different. We also investigated the similarity in microbial composition between healthy controls and SG without Helicobacter pylori infection, but not in those with H. pylori infection. According to the linear discriminant analysis effect size and random forest analyses, Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between SG and AG (AG_N) without H. pylori infection, whereas Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. We also found that the development of AG_N was associated with lower vitamin B12 levels, whereas significant changes in the gastric microbiota functions of AG_P included gallate, amino acid degradation, and heme biosynthesis. In addition, non-dialysis classifiers were developed for AG_N with an area under the curve (AUC) of 0.7417 and for AG_P with an AUC of 0.8862. This study thoroughly profiled the gastric microbiota of AG and SG and provided evidence of the potential of microbial markers as noninvasive classifiers for global AG.

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“…This formate accumulation during methylotrophic growth led to the postulation that formate could be utilized by oxidization to CO 2 for NADH generation as well as incorporation into the serine cycle. Moreover, it is also described that formaldehyde oxidation to formate in bacteria has a much greater capacity than methanol oxidation to avoid toxic formaldehyde accumulation [ 88 ].…”

Section: -Metabolism In Methylotrophic Yeastsmentioning

confidence: 99%

Synthetic methylotrophic yeasts for the sustainable fuel and chemical production

Wegat

Fabarius

Sieber

2022

Biotechnol Biofuels

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Global energy-related emissions, in particular carbon dioxide, are rapidly increasing. Without immediate and strong reductions across all sectors, limiting global warming to 1.5 °C and thus mitigating climate change is beyond reach. In addition to the expansion of renewable energies and the increase in energy efficiency, the so-called Carbon Capture and Utilization technologies represent an innovative approach for closing the carbon cycle and establishing a circular economy. One option is to combine CO2 capture with microbial C1 fermentation. C1-molecules, such as methanol or formate are considered as attractive alternative feedstock for biotechnological processes due to their sustainable production using only CO2, water and renewable energy. Native methylotrophic microorganisms can utilize these feedstock for the production of value-added compounds. Currently, constraints exist regarding the understanding of methylotrophic metabolism and the available genetic engineering tools are limited. For this reason, the development of synthetic methylotrophic cell factories based on the integration of natural or artificial methanol assimilation pathways in biotechnologically relevant microorganisms is receiving special attention. Yeasts like Saccharomyces cerevisiae and Yarrowia lipolytica are capable of producing important products from sugar-based feedstock and the switch to produce these in the future from methanol is important in order to realize a CO2-based economy that is independent from land use. Here, we review historical biotechnological applications, the metabolism and the characteristics of methylotrophic yeasts. Various studies demonstrated the production of a broad set of promising products from fine chemicals to bulk chemicals by applying methylotrophic yeasts. Regarding synthetic methylotrophy, the deep understanding of the methylotrophic metabolism serves as the basis for microbial strain engineering and paves the way towards a CO2-based circular bioeconomy. We highlight design aspects of synthetic methylotrophy and discuss the resulting chances and challenges using non-conventional yeasts as host organisms. We conclude that the road towards synthetic methylotrophic yeasts can only be achieved through a combination of methods (e.g., metabolic engineering and adaptive laboratory evolution). Furthermore, we presume that the installation of metabolic regeneration cycles such as supporting carbon re-entry towards the pentose phosphate pathway from C1-metabolism is a pivotal target for synthetic methylotrophy.

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Unravelling Formaldehyde Metabolism in Bacteria: Road towards Synthetic Methylotrophy

Cited by 15 publications

References 177 publications

Unique alcohol dehydrogenases involved in algal sugar utilization by marine bacteria

Unique alcohol dehydrogenases involved in algal sugar utilization by marine bacteria

A Meta-analysis Reveals Gastric Microbes Associated with Atrophic Gastritis

Synthetic methylotrophic yeasts for the sustainable fuel and chemical production

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