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.

Chemical Composition of Aerosols from the E-Cigarette Vaping of Natural and Synthetic Cannabinoids.

Vaping cannabinoids in electronic (e)-cigarette devices is rapidly increasing in popularity, particularly among adolescents, although the chemistry affecting the composition of the vape aerosol is not well understood. This work investigates the formation of aerosol mass, bioactive hydroxyquinones, and harmful or potentially harmful carbonyls from the e-cigarette vaping of natural and synthetic cannabinoids e-liquids in propylene glycol and vegetable glycerin (PG/VG) solvent at a 50 mg/mL concentration in a commercial fourth-generation vaping device. The following cannabinoids were studied: cannabidiol (CBD), 8,9-dihydrocannabidiol (H2CBD), 1,2,8,9-tetrahydrocannabidiol (H4CBD), cannabigerol (CBG), and cannabidiolic acid (CBDA).

Synthetic Biology of Natural Products Engineering: Recent Advances Across the Discover-Design-Build-Test-Learn Cycle.

Advances in genome engineering and associated technologies have reinvigorated natural products research. Here we highlight the latest developments in the field across the discover-design-build-test-learn cycle of bioengineering, from recent progress in computational tools for AI-supported genome mining, enzyme and pathway engineering, and compound identification to novel host systems and new techniques for improving production levels, and place these trends in the context of responsible research and innovation, emphasizing the importance of anticipatory analysis at the early stages of process development.

The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin.

With the rise in antimicrobial resistance, there is an urgent need for new classes of antibiotic with which to treat infectious disease. Marinomycin, a polyene antibiotic from a marine microbe, has been shown capable of killing methicillin-resistant (MRSA) and vancomycin-resistant (VREF), as well as having promising activity against melanoma. An attractive solution to the photoprotection of this antibiotic has been demonstrated.

Expanding flavone and flavonol production capabilities in .

Flavones and flavonols are important classes of flavonoids with nutraceutical and pharmacological value, and their production by fermentation with recombinant microorganisms promises to be a scalable and economically favorable alternative to extraction from plant sources. Flavones and flavonols have been produced recombinantly in a number of microorganisms, with typically being a preferred production host for these compounds due to higher yields and titers of precursor compounds, as well as generally improved ability to functionally express cytochrome P450 enzymes without requiring modification to improve their solubility. Recently, a rapid prototyping platform has been developed for high-value compounds in , and a number of gatekeeper (2)-flavanones, from which flavones and flavonols can be derived, have been produced to high titers in using this platform.

Computational design and experimental analysis of a novel visor for COVID-19 patients receiving high-flow nasal oxygen therapy.

The Covid-19 global pandemic has reshaped the requirements of healthcare sectors worldwide. Following the exposure risks associated with Covid-19, this paper aims to design, optimise, and validate a wearable medical device that reduces the risk of transmission of contagious droplets from infected patients in a hospital setting. This study specifically focuses on those receiving high-flow nasal oxygen therapy.

Harnessing intercellular signals to engineer the soil microbiome.

Covering: Focus on 2015 to 2020Plant and soil microbiomes consist of diverse communities of organisms from across kingdoms and can profoundly affect plant growth and health. Natural product-based intercellular signals govern important interactions between microbiome members that ultimately regulate their beneficial or harmful impacts on the plant. Exploiting these evolved signalling circuits to engineer microbiomes towards beneficial interactions with crops is an attractive goal.

Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic sp.

Four unusual cyclopeptides, zelkovamycins B-E (-), were isolated from an endophytic sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations.

Photoplethysmographic evaluation of generalized tonic-clonic seizures.

Objective: Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic-clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection.

Methods: During electroencephalographic (EEG) long-term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals.

A marine viral halogenase that iodinates diverse substrates.

Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage.

Defining the genes for the final steps in biosynthesis of the complex polyketide antibiotic mupirocin by Pseudomonas fluorescens NCIMB10586.

The mupirocin trans-AT polyketide synthase pathway, provides a model system for manipulation of antibiotic biosynthesis. Its final phase involves removal of the tertiary hydroxyl group from pseudomonic acid B, PA-B, producing the fully active PA-A in a complex series of steps. To further clarify requirements for this conversion, we fed extracts containing PA-B to mutants of the producer strain singly deficient in each mup gene.

Non-invasive Seizure Localization with Ictal Single-Photon Emission Computed Tomography is Impacted by Preictal/Early Ictal Network Dynamics.

Objective: More than one third of children with epilepsy have medically intractable seizures. Promising therapies, including targeted neurostimulation and surgery, depend on accurate localization of the epileptogenic zone. Ictal perfusion Single-Photon Emission Computed Tomography (SPECT) can localize the seizure focus noninvasively, with comparable accuracy to that of invasive EEG.

Fine Tuning of Antibiotic Activity by a Tailoring Hydroxylase in a Trans-AT Polyketide Synthase Pathway.

The addition or removal of hydroxy groups modulates the activity of many pharmacologically active biomolecules. It can be integral to the basic biosynthetic factory or result from associated tailoring steps. For the anti-MRSA antibiotic mupirocin, removal of a C8-hydroxy group late in the biosynthetic pathway gives the active pseudomonic acid A.

Selected Mutations Reveal New Intermediates in the Biosynthesis of Mupirocin and the Thiomarinol Antibiotics.

Thiomarinol and mupirocin are assembled on similar polyketide/fatty acid backbones and exhibit potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA). They both contain a tetrasubstituted tetrahydropyran (THP) ring that is essential for biological activity. Mupirocin is a mixture of pseudomonic acids (PAs).

Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes.

Chemical probes capable of reacting with KS (ketosynthase)-bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6-methylsalicylic acid synthase (6-MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6-MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6-MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities.

Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes.

Chemical probes capable of reacting with KS (ketosynthase)-bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6-methylsalicylic acid synthase (6-MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6-MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6-MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities.

Expression of different bacterial cytotoxins is controlled by two global transcription factors, CRP and Fis, that co-operate in a shared-recruitment mechanism.

Pet is a cytotoxic autotransporter protein secreted by the pathogenic enteroaggregative Escherichia coli strain 042. Expression of Pet is co-dependent on two global transcription regulators: CRP (cyclic AMP receptor protein) and Fis (factor for inversion stimulation). At the pet promoter CRP binds to a single site centred at position -40.

Electron transfer mechanism in Shewanella loihica PV-4 biofilms formed at graphite electrode.

Electron transfer mechanisms in Shewanella loihica PV-4 viable biofilms formed at graphite electrodes were investigated in potentiostat-controlled electrochemical cells poised at oxidative potentials (0.2V vs. Ag/AgCl).

Patient-specific seizure onset detection.

This paper presents an automated, patient-specific method for the detection of epileptic seizure onsets from noninvasive EEG. We adopt a patient-specific approach to exploit the consistency of an individual patient's seizure and non-seizure EEG. Our method uses a wavelet decomposition to construct a feature vector that captures the morphology and spatial distribution of an EEG epoch, and then determines whether that vector is representative of a patient's seizure or non-seizure EEG using the support-vector machine classification algorithm.

Patient-specific seizure onset detection.

This article presents an automated, patient-specific method for the detection of epileptic seizure onset from noninvasive electroencephalography. We adopt a patient-specific approach to exploit the consistency of an individual patient's seizure and nonseizure electroencephalograms. Our method uses a wavelet decomposition to construct a feature vector that captures the morphology and spatial distribution of an electroencephalographic epoch, and then determines whether that vector is representative of a patient's seizure or nonseizure electroencephalogram using the support vector machine classification algorithm.