Identification and Reconstitution of the First Two Enzymatic Steps for the Biosynthesis of Bioactive Meroterpenoids from (Lion's Mane Mushroom).

(Lion's Mane mushroom) is widely consumed for its numerous reported benefits for brain health. A growing body of evidence suggests that these benefits are likely attributable to aromatic compounds contained in its fruiting bodies, including the meroterpenoids hericenones. Here, we report the identification and reconstitution of the first two steps of the biosynthetic pathway of hericenones via heterologous expression of the polyketide synthase HerA and the carboxylic acid reductase HerB in .

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.

Discovery and Heterologous Expression of Functional 4--Dimethylallyl-l-tyrosine Synthases from Lichen-Forming Fungi.

Fungal aromatic prenyltransferases are a family of biosynthetic enzymes that catalyze the prenylation of a range of aromatic substrates during the biosynthesis of bioactive indole alkaloids, diketopiperazines, and meroterpenoids. Their broad substrate scope and soluble nature make these enzymes particularly adept for applications in biocatalysis; for example, the enzymatic derivatization of aromatic drugs improves their bioactivity. Here, we investigated four putative aromatic prenyltransferases from lichen-forming fungi, an underexplored group of organisms that produce more than 1,000 unique metabolites.

Genome sequencing and molecular networking analysis of the wild fungus Anthostomella pinea reveal its ability to produce a diverse range of secondary metabolites.

Background: Filamentous fungi are prolific producers of bioactive molecules and enzymes with important applications in industry. Yet, the vast majority of fungal species remain undiscovered or uncharacterized. Here we focus our attention to a wild fungal isolate that we identified as Anthostomella pinea.

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids.

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers.

Heterologous Naringenin Production in the Filamentous Fungus .

Naringenin is a natural product with several reported bioactivities and is the key intermediate for the entire class of plant flavonoids. The translation of flavonoids into modern medicine as pure compounds is often hampered by their low abundance in nature and their difficult chemical synthesis. Here, we investigated the possibility to use the filamentous fungus as a host for flavonoid production.

Design and engineering of artificial biosynthetic pathways-where do we stand and where do we go?

The production of commodity and specialty chemicals relies heavily on fossil fuels. The negative impact of this dependency on our environment and climate has spurred a rising demand for more sustainable methods to obtain such chemicals from renewable resources. Herein, biotransformations of these renewable resources facilitated by enzymes or (micro)organisms have gained significant attention, since they can occur under mild conditions and reduce waste.

Genomic and Metabolomic Analysis of the Endophytic Fungus sp. VM-40 Isolated from the Medicinal Plant .

The genus is well-known to comprise many pathogenic fungi that affect cereal crops worldwide, causing severe damage to agriculture and the economy. In this study, an endophytic fungus designated sp. VM-40 was isolated from a healthy specimen of the traditional European medicinal plant .

Structural Characterization and Extended Substrate Scope Analysis of Two Mg -Dependent O-Methyltransferases from Bacteria.

Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we characterized the enzymatic properties and substrate scope of two bacterial OMTs from Desulforomonas acetoxidans and Streptomyces avermitilis and determined their crystal structures.

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC.

Striving for sustainable biosynthesis: discovery, diversification, and production of antimicrobial drugs in Escherichia coli.

New antimicrobials need to be discovered to fight the advance of multidrug-resistant pathogens. A promising approach is the screening for antimicrobial agents naturally produced by living organisms. As an alternative to studying the native producer, it is possible to use genetically tractable microbes as heterologous hosts to aid the discovery process, facilitate product diversification through genetic engineering, and ultimately enable environmentally friendly production.

spp. in Austria-The Tick, the Climate, the Diseases and the Risk for Humans and Animals.

Recently, ticks of spp. have been found more often in areas previously lacking this tick species. Due to their important role as a vector of different diseases, such as Crimean-Congo-hemorrhagic fever (CCHF), the occurrence and potential spread of this tick species is of major concern.

Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease.

Background And Aims: Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described.

Approach And Results: Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included.

Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients.

Background And Aims: The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups.

Methods: Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included.

Artemisinin-Type Drugs in Tumor Cell Death: Mechanisms, Combination Treatment with Biologics and Nanoparticle Delivery.

Artemisinin, the most famous anti-malaria drug initially extracted from L., also exhibits anti-tumor properties in vivo and in vitro. To improve its solubility and bioavailability, multiple derivatives have been synthesized.

Changing summer precipitation variability in the Alpine region: on the role of scale dependent atmospheric drivers.

Summer precipitation totals in the Alpine Region do not exhibit a systematic trend over the last 120 years. However, we find significant low frequency periodicity of interannual variability which occurs in synchronization with a dominant two-phase state of the atmospheric circulation over the Alps. Enhanced meridional flow increases precipitation variability through positive soil moisture precipitation feedbacks on the regional scale, whereas enhanced zonal flow results in less variability through constant moisture flow from the Atlantic and suppressed feedbacks with the land surface.

Rapid in vitro prototyping of O-methyltransferases for pathway applications in Escherichia coli.

O-Methyltransferases are ubiquitous enzymes involved in biosynthetic pathways for secondary metabolites such as bacterial antibiotics, human catecholamine neurotransmitters, and plant phenylpropanoids. While thousands of putative O-methyltransferases are found in sequence databases, few examples are functionally characterized. From a pathway engineering perspective, however, it is crucial to know the substrate and product ranges of the respective enzymes to fully exploit their catalytic power.

Current State and Future Directions of Genetics and Genomics of Endophytic Fungi for Bioprospecting Efforts.

The bioprospecting of secondary metabolites from endophytic fungi received great attention in the 1990s and 2000s, when the controversy around taxol production from spp. endophytes was at its height. Since then, hundreds of reports have described the isolation and characterization of putative secondary metabolites from endophytic fungi.

Natural combinatorial genetics and prolific polyamine production enable siderophore diversification in Serratia plymuthica.

Background: Iron is essential for bacterial survival. Bacterial siderophores are small molecules with unmatched capacity to scavenge iron from proteins and the extracellular milieu, where it mostly occurs as insoluble Fe. Siderophores chelate Fe for uptake into the cell, where it is reduced to soluble Fe.

Current European flood-rich period exceptional compared with past 500 years.

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective.

Heterologous caffeic acid biosynthesis in Escherichia coli is affected by choice of tyrosine ammonia lyase and redox partners for bacterial Cytochrome P450.

Background: Caffeic acid is industrially recognized for its antioxidant activity and therefore its potential to be used as an anti-inflammatory, anticancer, antiviral, antidiabetic and antidepressive agent. It is traditionally isolated from lignified plant material under energy-intensive and harsh chemical extraction conditions. However, over the last decade bottom-up biosynthesis approaches in microbial cell factories have been established, that have the potential to allow for a more tailored and sustainable production.

Disentangling Drivers of Meteorological Droughts in the European Greater Alpine Region During the Last Two Centuries.

This study investigates the atmospheric drivers of severe precipitation deficits in the Greater Alpine Region during the last 210 years utilizing a daily atmospheric circulation type reconstruction. Precipitation deficit tends to be higher during periods with more frequent anticyclonic (dry) and less frequent cyclonic (wet) circulation types, as would be expected. However, circulation characteristics are not the main drivers of summer precipitation deficit.

Coupled effects of wind-storms and drought on tree mortality across 115 forest stands from the Western Alps and the Jura mountains.

Damage due to wind-storms and droughts is increasing in many temperate forests, yet little is known about the long-term roles of these key climatic factors in forest dynamics and in the carbon budget. The objective of this study was to estimate individual and coupled effects of droughts and wind-storms on adult tree mortality across a 31-year period in 115 managed, mixed coniferous forest stands from the Western Alps and the Jura mountains. For each stand, yearly mortality was inferred from management records, yearly drought from interpolated fields of monthly temperature, precipitation and soil water holding capacity, and wind-storms from interpolated fields of daily maximum wind speed.

Regulation of the P450 Oxygenation Cascade Involved in Glycopeptide Antibiotic Biosynthesis.

Glycopeptide antibiotics (GPAs) are nonribosomal peptides rich in modifications introduced by external enzymes. These enzymes act on the free peptide aglycone or intermediates bound to the nonribosomal peptide synthetase (NRPS) assembly line. In this process the terminal module of the NRPS plays a crucial role as it contains a unique recruitment platform (X-domain) interacting with three to four modifying Cytochrome P450 (P450) enzymes that are responsible for cyclizing bound peptides.