α-Pyrrolidinohexanophenone (α-PHP) and α-Pyrrolidinoisohexanophenone (α-PiHP): A Review.

New Psychoactive Substances are currently a serious and growing problem affecting public health worldwide. By 2022, 1184 of these substances had been identified over a period of 16 years. Within these, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP) have emerged, two synthetic cathinones from the pyrovalerone derivates subgroup that are positional isomers of each other.

Divergence of Classical and C-Ring-Cleaved Angucyclines: Elucidation of Early Tailoring Steps in Lugdunomycin and Thioangucycline Biosynthesis.

Angucyclines are an important group of microbial natural products that display tremendous chemical diversity. Classical angucyclines are composed of a tetracyclic benz[]anthracene scaffold with one ring attached at an angular orientation. However, in atypical angucyclines, the polyaromatic aglycone is cleaved at A-, B-, or C-rings, leading to structural rearrangements and enabling further chemical variety.

Evolution-inspired engineering of anthracycline methyltransferases.

soil bacteria produce hundreds of anthracycline anticancer agents with a relatively conserved set of genes. This diversity depends on the rapid evolution of biosynthetic enzymes to acquire novel functionalities. Previous work has identified -adenosyl-l-methionine-dependent methyltransferase-like proteins that catalyze 4-O-methylation, 10-decarboxylation, or 10-hydroxylation, with additional differences in substrate specificities.

The Rural Fires of 2017 and Their Influences on Water Quality: An Assessment of Causes and Effects.

As water is facing increasing pressures from population and economic growth and climate change, it becomes imperative to promote the protection, restoration and management of this resource and its watersheds. Since water quality depends on multiple factors both natural and anthropic, it is not easy to establish their influences. After the October 2017 fires that affected almost 30% of the Mondego hydrographic basin in Central Portugal, 10 catchments were selected for periodic physical-chemical monitoring.

Sources of Potentially Toxic Elements in Sediments of the Mussulo Lagoon (Angola) and Implications for Human Health.

The Mussulo lagoon is a coastal environment located near Luanda, one of the SW African cities that has been growing more rapidly during the last decades. Geochemical, mineralogical, and grain-size data obtained for the lagoon sediments are analyzed together, in order to establish the factors that control the distribution of some potentially toxic elements (PTEs). Sediments from northern location tend to be enriched in feldspar and, despite some variability in grain-size distributions, in fine-grained detrital minerals; southern lagoon sediments display very homogenous grain-size distribution and are enriched in minerals associated with salt precipitation (halite and gypsum).

Evolution-guided engineering of non-heme iron enzymes involved in nogalamycin biosynthesis.

Microbes are competent chemists that are able to generate thousands of chemically complex natural products with potent biological activities. The key to the formation of this chemical diversity has been the rapid evolution of secondary metabolism. Many enzymes residing on these metabolic pathways have acquired atypical catalytic properties in comparison with their counterparts found in primary metabolism.

Links between Cognitive Status and Trace Element Levels in Hair for an Environmentally Exposed Population: A Case Study in the Surroundings of the Estarreja Industrial Area.

In the present study, trace elements (TE) levels were evaluated in scalp hair along the continuum from healthy subjects (HS) to patients suffering from subjective memory concerns (SMC), and/or mild cognitive impairment (MCI), and those with already installed dementia (DEM) in order to: (i) assess the effects of environmental and lifestyle factors on TE concentrations and (ii) evaluate the analyzed elements as possible diagnostic biomarkers for the disease. The study involved 79 mainly permanent residents, >55 years old, from the city of Estarreja (northern Portugal), a former industrial area. The health status of the participants was assessed by means of a complete socio-demographic questionnaire and through cognitive screening tests, namely the Mini-Mental State Examination (MMSE).

Human predisposition to cognitive impairment and its relation with environmental exposure to potentially toxic elements.

New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson's, Alzheimer's and sclerosis diseases. This study proposes a multidisciplinary approach combining neurosciences, psychology and environmental sciences while integrating socio-economic, neuropsychological, environmental and health data.

Metallocofactor assembly for [FeFe]-hydrogenases.

Hydrogenases are a potential source of environmentally benign bioenergy, using complex cofactors to catalyze the reversible reduction of protons to form hydrogen. The most active subclass, the [FeFe]-hydrogenases, is dependent on a metallocofactor, the H cluster, that consists of a two iron subcluster ([2Fe]) bridging to a classical cubane cluster ([4Fe-4S]). The ligands coordinating to the diiron subcluster include an azadithiolate, three carbon monoxides, and two cyanides.

Divergent evolution of an atypical S-adenosyl-l-methionine-dependent monooxygenase involved in anthracycline biosynthesis.

Bacterial secondary metabolic pathways are responsible for the biosynthesis of thousands of bioactive natural products. Many enzymes residing in these pathways have evolved to catalyze unusual chemical transformations, which is facilitated by an evolutionary pressure promoting chemical diversity. Such divergent enzyme evolution has been observed in S-adenosyl-L-methionine (SAM)-dependent methyltransferases involved in the biosynthesis of anthracycline anticancer antibiotics; whereas DnrK from the daunorubicin pathway is a canonical 4-O-methyltransferase, the closely related RdmB (52% sequence identity) from the rhodomycin pathways is an atypical 10-hydroxylase that requires SAM, a thiol reducing agent, and molecular oxygen for activity.

X-ray crystallographic and EPR spectroscopic analysis of HydG, a maturase in [FeFe]-hydrogenase H-cluster assembly.

Hydrogenases use complex metal cofactors to catalyze the reversible formation of hydrogen. In [FeFe]-hydrogenases, the H-cluster cofactor includes a diiron subcluster containing azadithiolate, three CO, and two CN(-) ligands. During the assembly of the H cluster, the radical S-adenosyl methionine (SAM) enzyme HydG lyses the substrate tyrosine to yield the diatomic ligands.

Structures of lipoyl synthase reveal a compact active site for controlling sequential sulfur insertion reactions.

Lipoyl cofactors are essential for living organisms and are produced by the insertion of two sulfur atoms into the relatively unreactive C-H bonds of an octanoyl substrate. This reaction requires lipoyl synthase, a member of the radical S-adenosylmethionine (SAM) enzyme superfamily. In the present study, we solved crystal structures of lipoyl synthase with two [4Fe-4S] clusters bound at opposite ends of the TIM barrel, the usual fold of the radical SAM superfamily.