Evaluation of Yeast Alcohol Acetyltransferases for Ethyl Acetate Production in .

Sustainable chemical production from C gaseous substrates, such as syngas or CO/H, can be achieved through gas fermentation. In gas fermentation, acetogenic bacteria are able to utilize oxidized inorganic carbon sources as the sole carbon source and electron acceptor, while reduced inorganic species are used as the electron donor. , a model acetogen, is only capable of reducing CO to acetate and ethanol, with H as electron donor.

Lactic acid in the vaginal milieu modulates the -host interaction.

Vulvovaginal candidiasis (VVC) is one of the most common infections caused by . VVC is characterized by an inadequate hyperinflammatory response and clinical symptoms associated with colonization of the vaginal mucosa. Compared to other host niches in which can cause infection, the vaginal environment is extremely rich in lactic acid that is produced by the vaginal microbiota.

Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease.

Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases.

Results: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis.

Microbial adaptive pathogenicity strategies to the host inflammatory environment.

Pathogenic microorganisms can infect a variety of niches in the human body. During infection, these microbes can only persist if they adapt adequately to the dynamic host environment and the stresses imposed by the immune system. While viruses entirely rely on host cells to replicate, bacteria and fungi use their pathogenicity mechanisms for the acquisition of essential nutrients that lie under host restriction.

Role of amino acid substitutions on proteolytic stability of histatin 5 in the presence of secreted aspartyl proteases and salivary proteases.

Histatin 5 (Hst5) is a 24-amino-acid peptide naturally present in human saliva that has been proposed as a potential antifungal therapeutic. However, Hst5 is susceptible to degradation by secreted aspartyl proteases (Saps) produced by Candida albicans, which could limit its efficacy as a therapeutic. To better understand the role of the lysine residues of Hst5 in proteolysis by C.

tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus.

Increasing antifungal drug resistance is a major concern associated with human fungal pathogens like Aspergillus fumigatus. Genetic mutation and epimutation mechanisms clearly drive resistance, yet the epitranscriptome remains relatively untested. Here, deletion of the A.

The palmitoyl-CoA ligase Fum16 is part of a fumonisin subcluster involved in self-protection.

produces the mycotoxin fumonisin B (FB), which disrupts sphingolipid biosynthesis by inhibiting ceramide synthase and affects the health of plants, animals, and humans. The means by which protects itself from its own mycotoxin are not completely understood. Some fumonisin () cluster genes do not contribute to the biosynthesis of the compound, but their function has remained enigmatic.

Accessing microbial natural products of the past.

Microbial natural products-low molecular weight compounds biosynthesized by microorganisms-form the foundation of important modern therapeutics, including antibiotics, immunomodulators, and anti-cancer agents. This perspective discusses and contrasts two emerging approaches for uncovering natural products of the past. On the one hand, ancestral sequence reconstruction allows recreating biosynthetic pathways that date back hundreds of millions of years.

Tracking the uptake of labelled host-derived extracellular vesicles by the human fungal pathogen .

Extracellular vesicles (EVs) have gained attention as facilitators of intercellular as well as interkingdom communication during host-microbe interactions. Recently we showed that upon infection, host polymorphonuclear leukocytes produce antifungal EVs targeting the clinically important fungal pathogen ; however, the small size of EVs (<1 µm) complicates their functional analysis. Here, we employed a more tractable, reporter-based system to label host alveolar epithelial cell-derived EVs and enable their visualization during interaction.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Spatiotemporal modeling quantifies cellular contributions to uptake of Aspergillus fumigatus in the human lung.

The human lung is confronted daily with thousands of microbial invaders reaching the lower respiratory tract. An efficient response by the resident type 1 and type 2 alveolar epithelial cells (AECs) and alveolar macrophages (AMs) cells during the early hours of innate immunity is a prerequisite to maintain a non-inflammatory state, but foremost to rapidly remove harmful substances. One such human-pathogenic invader is the opportunistic fungus Aspergillus fumigatus.

Alpha-1-antitrypsin as novel substrate for Spl proteases - implications for virulence.

Background: The serine protease like (Spl) proteases of are a family of six proteases whose function and impact on virulence are poorly understood. Here we propose alpha-1-antitrypsin (AAT), an important immunomodulatory serine protease inhibitor as target of SplD, E and F. AAT is an acute phase protein, interacting with many proteases and crucial for prevention of excess tissue damage by neutrophil elastase during the innate immune response to infections.

FungiFun3: systemic gene set enrichment analysis for fungal species.

Summary: The ever-growing amount of genome-wide omics data paved the way for solving life science problems in a data-driven manner. Among others, enrichment analysis is part of the standard analysis arsenal to determine systemic signals in any given transcriptomic or proteomic data. Only a part of the members of the fungal kingdom, however, can be analyzed via public web applications, despite the global rise of fungal pathogens and their increasing resistance to antimycotics.

Leveraging Organ-on-Chip Models to Investigate Host-Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice.

Optimized psilocybin production in tryptophan catabolism-repressed fungi.

The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy-refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a 'Breakthrough Therapy' by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an in vivo psilocybin production chassis based on repression of l-tryptophan catabolism.

Saccharomyces boulardii enhances anti-inflammatory effectors and AhR activation via metabolic interactions in probiotic communities.

Metabolic exchanges between strains in gut microbial communities shape their composition and interactions with the host. This study investigates the metabolic synergy between potential probiotic bacteria and Saccharomyces boulardii, aiming to enhance anti-inflammatory effects within a multi-species probiotic community. By screening a collection of 85 potential probiotic bacterial strains, we identified two strains that demonstrated a synergistic relationship with S.

ProcCluster® and procaine hydrochloride inhibit the growth of species and exert antimicrobial properties during coinfection with influenza A viruses and .

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant strains can complicate antifungal therapy.

Alligamycin A, an antifungal β-lactone spiroketal macrolide from Streptomyces iranensis.

Fungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches.

The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site.

The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM and PsiM, were generated to further examine the role of Asn247 for mono- and dimethylation in PsiM.

Shining a light on -induced epithelial damage with a luciferase reporter.

Host cell damage is a key parameter for research in infection biology, drug testing, and substance safety screening. In this study, we introduce a luciferase reporter system as a new and reliable assay to measure cell damage and validate it with the pathogenic yeast, , as a test case. We transduced human epithelial cell lines with a lentiviral vector to stably express an optimized luciferase enzyme, Nanoluc.

Comparative genomics unravels a rich set of biosynthetic gene clusters with distinct evolutionary trajectories across fungal species (Termitomyces) farmed by termites.

The use of compounds produced by hosts or symbionts for defence against antagonists has been identified in many organisms, including in fungus-farming termites (Macrotermitinae). The obligate mutualistic fungus Termitomyces plays a pivotal role in plant biomass decomposition and as the primary food source for these termites. Despite the isolation of various specialized metabolites from different Termitomyces species, our grasp of their natural product repertoire remains incomplete.