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A diverse spectrum of organisms, such as fungi, bacteria, and actinomycetes, can degrade and transform organic matter, including wood, into valuable nutrients. A sustainable economy has the goal of efficiently using waste as raw materials, and in this optic, it uses biological preparations more and more often, supporting the decomposition of lignocellulosic waste. With reference to wood wastes, which are produced in a substantial amount by the forest and wood industry, one of the possibilities to biodegrade such lignocellulosic material is the composting process. In particular, microbiological inoculum containing dedicated fungi can contribute to the biodegradation of wood waste, as well as the biotransformation of substances from the protection of wood, such as pentachlorophenol (PCP), lindane (hexachlorobenzene) and polycyclic aromatic hydrocarbons (PAHs). The purpose of this research was to produce a literature review in terms of the selection of decay fungi that could potentially be used in toxic biotransformation unions. The findings of the literature review highlighted how fungi such as Bjerkandera adusta, Phanerochaete chrysosporium, and Trametes versicolor might be ingredients of biological consortia that can be effectively applied in composting wood waste containing substances such as pentachlorophenol, lindane, and polycyclic aromatic hydrocarbons (PAHs).

Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.

Arsenic, distributed pervasively in the natural environment, is an extremely toxic substance which can severely impair the normal functions of living cells. Research on the genetic mechanisms of arsenic metabolism is of great importance for remediating arsenic-contaminated environments. Many organisms, including bacteria, have developed various strategies to tolerate arsenic, by either detoxifying this harmful element or utilizing it for energy generation. This review summarizes arsenic detoxification as well as arsenic respiratory metabolic pathways in bacteria and discusses novel arsenic resistance pathways in various bacterial strains. This knowledge provides insights into the mechanisms of arsenic biotransformation in bacteria. Multiple detoxification strategies among bacteria imply possible functional relationships among different arsenic detoxification/metabolism pathways. In addition, this review sheds light on the bioremediation of arsenic-contaminated environments and prevention of antibiotic resistance.

‘Ideal’ solvents in biocatalysis have to fulfill a large number of requirements, such as high substrate solubility, high enzyme activity and stability, and positive effects on reaction equilibrium. In the past decades, many enzymatic synthesis routes in water-based and nonaqueous (organic solvents, ionic or supercritical fluids) reaction media have been developed. However, no solvent meets every demand for different reaction types at the same time, and there is still a need for novel solvents suited for different reaction types and applications. Deep eutectic solvents (DESs) have recently been evaluated as solvents in different biocatalytic reactions. They can improve substrate supply, conversion, and stability. The best results were obtained when the DES is formed by the substrates of an enzymatic reaction. A wide range of inexpensive renewables can be used as components of deep eutectic solvents; therefore, the solvents are often biodegradable, nontoxic, nonvolatile, and nonflammable. A broad range of enzymatic and chemo-enzymatic synthesis reactions can be performed in deep eutectic solvents. Most of the reactions, covering transesterifications, epoxidations, and C–C bond formations, are catalyzed by lipases. Deep eutectic solvents can be used to enable new biocatalytic synthesis routes that cannot be realized in conventional reaction media (i.e., aqueous buffers). Components of deep eutectic solvents can be used as substrate and solvent at the same time; this virtually solvent-free approach enables processes with high substrate conversion and high atom efficiency.

Pyrrolizidine alkaloids (PAs) are among the most significant groups of phytotoxins present in more than 6000 plants in the world. Hepatotoxic retronecine-type PAs and their corresponding N-oxides usually co-exist in plants. Although PA-induced hepatotoxicity is known for a long time and has been extensively studied, the toxicity of PA N-oxide is rarely investigated. Recently, we reported PA N-oxide-induced hepatotoxicity in humans and rodents and also suggested the association of such toxicity with metabolic conversion of PA N-oxides to the corresponding toxic PAs. However, the detailed biochemical mechanism of PA N-oxide-induced hepatotoxicity is largely unknown. The present study investigated biotransformation of four representative cyclic retronecine-type PA N-oxides to their corresponding PAs in both gastrointestinal tract and liver. The results demonstrated that biotransformation of PA N-oxides to PAs was mediated by both intestinal microbiota and hepatic cytochrome P450 monooxygenases (CYPs), in particular CYP1A2 and CYP2D6. Subsequently, the formed PAs were metabolically activated predominantly by hepatic CYPs to form reactive metabolites exerting hepatotoxicity. Our findings delineated, for the first time, that the metabolism-mediated mechanism of PA N-oxide intoxication involved metabolic reduction of PA N-oxides to their corresponding PAs in both intestine and liver followed by oxidative bioactivation of the resultant PAs in the liver to generate reactive metabolites which interact with cellular proteins leading to hepatotoxicity. In addition, our results raised a public concern and also encouraged further investigations on potentially remarkable variations in PA N-oxide-induced hepatotoxicity caused by significantly altered intestinal microbiota due to individual differences in diets, life styles, and medications.

Background In the biochemical milieu of human colon, bile acids act as signaling mediators between the host and its gut microbiota. Biotransformation of primary to secondary bile acids have been known to be involved in the immune regulation of human physiology. Several 16S amplicon-based studies with inflammatory bowel disease (IBD) subjects were found to have an association with the level of fecal bile acids. However, a detailed investigation of all the bile salt biotransformation genes in the gut microbiome of healthy and IBD subjects has not been performed. Results Here, we report a comprehensive analysis of the bile salt biotransformation genes and their distribution at the phyla level. Based on the analysis of shotgun metagenomes, we found that the IBD subjects harbored a significantly lower abundance of these genes compared to the healthy controls. Majority of these genes originated from Firmicutes in comparison to other phyla. From metabolomics data, we found that the IBD subjects were measured with a significantly low level of secondary bile acids and high levels of primary bile acids compared to that of the healthy controls. Conclusions Our bioinformatics-driven approach of identifying bile salt biotransformation genes predicts the bile salt biotransformation potential in the gut microbiota of IBD subjects. The functional level of dysbiosis likely contributes to the variation in the bile acid pool. This study sets the stage to envisage potential solutions to modulate the gut microbiome with the objective to restore the bile acid pool in the gut.

Recently, several studies have proven the potential of cyanobacteria as whole-cell biocatalysts for biotransformation. Compared to heterotrophic hosts, cyanobacteria show unique advantages thanks to their photoautotrophic metabolism. Their ability to use light as energy and CO2 as carbon source promises a truly sustainable production platform. Their photoautotrophic metabolism offers an encouraging source of reducing power, which makes them attractive for redox-based biotechnological purposes. To exploit the full potential of these whole-cell biocatalysts, cyanobacterial cells must be considered in their entirety. With this emphasis, this review summarizes the latest developments in cyanobacteria research with a strong focus on the benefits associated with their unique metabolism. Remaining bottlenecks and recent strategies to overcome them are evaluated for their potential in future applications. Cyanobacteria use photosynthesis to harvest the Sun’s energy to bind atmospheric CO2 and accumulate biomass. This ability renders cyanobacteria interesting hosts for sustainable industrial processes.The photoautotrophic metabolism allows a constant supply with oxygen and NADPH, and so overcoming limitations, often faced in biotransformation with heterotrophic hosts.Compared to established biocatalysis hosts, cyanobacteria lag several years of development. Exploitation of their metabolism, especially of the photosynthesis apparatus, still shows room for improvement.Many aspects for whole-cell catalysis have not been investigated carefully enough, including mass transfer of substrate and product or tolerance towards stressors, such as solvents or ROS.Novel photo-bioreactor concepts and also new, and more efficient strains must be introduced to achieve economically feasible production.

Utilizing C1 feedstocks as the carbon source for microbial fermentation represents a powerful approach for alleviating the energy and food crises.Pichia pastoris has been developed as a promising chemical production chassis for carbon-neutral or even carbon-negative biomanufacturing.The development of synthetic biology has enabled the rational design of the metabolic network of P. pastoris and chemicals production with methanol as the sole carbon source.Coupling electrocatalysis with methylotrophic or formatotrophic-based microbial fermentation may be a viable proposal to achieve CO2 recovery. Bioconversion of C1 feedstocks for chemical production offers a promising solution to global challenges such as the energy and food crises and climate change. The methylotroph Pichia pastoris is an attractive host system for the production of both recombinant proteins and chemicals from methanol. Recent studies have also demonstrated its potential for utilizing CO2 through metabolic engineering or coupling with electrocatalysis. This review focuses on the bioconversion of C1 feedstocks for chemical production using P. pastoris. Herein the challenges and feasible strategies for chemical production in P. pastoris are discussed. The potential of P. pastoris to utilize other C1 feedstocks – including CO2 and formate – is highlighted, and new insights from the perspectives of synthetic biology and material science are proposed.

Gut microbes play a crucial role in transforming primary bile acids (BAs) into secondary forms, which influence systemic metabolic processes. The rumen, a distinctive and critical microbial habitat in ruminants, boasts a diverse array of microbial species with multifaceted metabolic capabilities. There remains a gap in our understanding of BA metabolism within this ecosystem. Herein, through the analysis of 9371 metagenome-assembled genomes and 329 cultured organisms from the rumen, we identified two enzymes integral to BA metabolism: 3-dehydro-bile acid delta4,6-reductase (baiN) and the bile acid:Na + symporter family (BASS). Both in vitro and in vivo experiments were employed by introducing exogenous BAs. We revealed a transformation of BAs in rumen and found an enzyme cluster, including L-ribulose-5-phosphate 3-epimerase and dihydroorotate dehydrogenase. This cluster, distinct from the previously known BA-inducible operon responsible for 7α-dehydroxylation, suggests a previously unrecognized pathway potentially converting primary BAs into secondary BAs. Moreover, our in vivo experiments indicated that microbial BA administration in the rumen can modulate amino acid and lipid metabolism, with systemic impacts underscored by core secondary BAs and their metabolites. Our study provides insights into the rumen microbiome’s role in BA metabolism, revealing a complex microbial pathway for BA biotransformation and its subsequent effect on host metabolic pathways, including those for glucose, amino acids, and lipids. This research not only advances our understanding of microbial BA metabolism but also underscores its wider implications for metabolic regulation, offering opportunities for improving animal and potentially human health. Graphical Abstract Graphical Abstract

The kidneys integrate information from continuous systemic processes related to the absorption, distribution, metabolism and excretion (ADME) of metabolites. To identify underlying molecular mechanisms, we performed genome-wide association studies of the urinary concentrations of 1,172 metabolites among 1,627 patients with reduced kidney function. The 240 unique metabolite–locus associations (metabolite quantitative trait loci, mQTLs) that were identified and replicated highlight novel candidate substrates for transport proteins. The identified genes are enriched in ADME-relevant tissues and cell types, and they reveal novel candidates for biotransformation and detoxification reactions. Fine mapping of mQTLs and integration with single-cell gene expression permitted the prioritization of causal genes, functional variants and target cell types. The combination of mQTLs with genetic and health information from 450,000 UK Biobank participants illuminated metabolic mediators, and hence, novel urinary biomarkers of disease risk. This comprehensive resource of genetic targets and their substrates is informative for ADME processes in humans and is relevant to basic science, clinical medicine and pharmaceutical research. Genome-wide association analysis of 1,172 urinary metabolites identifies 240 metabolite–locus associations that when combined with UK Biobank data suggest novel metabolic mediators of disease and markers of disease risk.