Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering ...of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo–mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration. The anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions.
The use of enzymes as catalysts for the preparation of novel compounds has received steadily increasing attention over the past few years. High demands are placed on the identification of new ...biocatalysts for organic synthesis. The catalysis of more ambitious reactions reflects the high expectations of this field of research. Enzymes play an increasingly important role as biocatalysts in the synthesis of key intermediates for the pharmaceutical and chemical industry, and new enzymatic technologies and processes have been established. Enzymes are an important part of the spectrum of catalysts available for synthetic chemistry. The advantages and applications of the most recent and attractive biocatalysts—reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases—will be discussed herein and exemplified by the syntheses of interesting compounds.
A dash of BIO‐catalyst: A new generation of biocatalysts has entered modern organic synthesis. Recent advances in enzyme catalysis for the synthesis of challenging chemicals are presented in this Review.
Glomalin is a glycoprotein produced by arbuscular mycorrhizal (AM) fungi, and the soil fraction containing glomalin is correlated with soil aggregation. Thus, factors potentially influencing glomalin ...production could be of relevance for this ecosystem process and for understanding AM fungal physiology. Previous work indicated that glomalin production in AM fungi may be a stress response, or related to suboptimal mycelium growth. We show here that environmental stress can enhance glomalin production in the mycelium of the AM fungus Glomus intraradices. We applied NaCl and glycerol in different intensities to the medium in which the fungus was grown in vitro, causing salinity stress and osmotic stress, respectively. As a third stress type, we simulated grazing on the extraradical hyphae of the fungus by mechanically injuring the mycelium by clipping. NaCl caused a strong increase, while the clipping treatment led to a marginally significant increase in glomalin production. Even though salinity stress includes osmotic stress, we found substantially different responses in glomalin production due to the NaCl and the glycerol treatment, as glycerol addition did not cause any response. Thus, our results indicate that glomalin is involved in inducible stress responses in AM fungi for salinity, and possibly grazing stress.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The study investigated the use of a Hardware-in-the-Loop (HiL) technique applied in model ice experiments to enable the analysis of offshore structures with low natural frequencies under dynamic ice ...loading. Traditional approaches were limited by facility capacities and ineffective downscaling of the geometry of the offshore structures. The goal of the present study was to overcome these challenges and to enhance the understanding and explore the applicability of a hybrid testing technique in model ice experiments. To achieve the objective, 204 Hardware-in-the-Loop simulations in model Ice (HiLI) were analyzed. Results showed robust behavior and good performance of the HiLI due to minimal variation in measured delay, normalized root mean square error, and peak tracking error and low magnitudes of such parameters despite alterations in factors such as the choice of the numerical structural model, physical prototype, measurement system, and ice type. Notably, the performance of the HiLI was affected when testing with warm model ice or scaling for harsh ice conditions, attributed to a reduced signal-to-noise ratio and instability of the system, respectively. Experimental identification of the critical delay, along with the application of an analytical stability criterion, revealed that the instability observed, was likely induced by reducing the structural stiffness of the numerical structural model to fulfil the scaling requirements when testing for harsh ice conditions. Additionally, the study showed improved HiLI performance when the physical prototype was in contact with the model ice. This observation was further analyzed and is assumed to be caused by the coupling between the ice and physical prototype, causing a coupled and thus increased eigenfrequency of the physical prototype-ice system.
Biochar application to soils has potential to simultaneously improve soil fertility and store carbon to aid climate change mitigation. While many studies have shown positive effects on plant yields, ...much less is known about the synergies between biochar and plant growth promoting microbes, such as mycorrhizal fungi. We present the first evidence that arbuscular mycorrhizal (AM) fungi can use biochar as a physical growth matrix and nutrient source. We used monoxenic cultures of the AM fungus Rhizophagus irregularis in symbiosis with carrot roots. Using scanning electron microscopy we observed that AM fungal hyphae grow on and into two contrasting types of biochar particles, strongly attaching to inner and outer surfaces. Loading a nutrient-poor biochar surface with nutrients stimulated hyphal colonization. We labeled biochar surfaces with 33P radiotracer and found that hyphal contact to the biochar surfaces permitted uptake of 33P and its subsequent translocation to the associated host roots. Direct access of fungal hyphae to biochar surfaces resulted in six times more 33P translocation to the host roots than in systems where a mesh prevented hyphal contact with the biochar.
We conclude that AM fungal hyphae access microsites within biochar, that are too small for most plant roots to enter (<10 μm), and can hence mediate plant phosphorus uptake from the biochar. Thus, combined management of biochar and AM fungi could contribute to sustainable soil and climate management by providing both a carbon-stable nutrient reservoir and a symbiont that facilitates nutrient uptake from it.
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•An arbuscular mycorrhizal fungus grows on and into different types of biochar.•Higher nutrient content of the biochar increases its fungal colonization.•Hyphal surface contact with biochar increases P transfer to the host plant six fold.
Soil is likely the most complex ecosystem on earth. Despite the global importance and extraordinary diversity of soils, they have been notoriously challenging to study. We show how pioneering ...microfluidic techniques provide new ways of studying soil microbial ecology by allowing simulation and manipulation of chemical conditions and physical structures at the microscale in soil model habitats.
In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, ...cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function.
Terpenoids are built from isoprene building blocks and have numerous biological functions. Selective late‐stage modification of their carbon scaffold has the potential to optimize or transform their ...biological activities. However, the synthesis of terpenoids with a non‐natural carbon scaffold is often a challenging endeavor because of the complexity of these molecules. Herein we report the identification and engineering of (S)‐adenosyl‐l‐methionine‐dependent sterol methyltransferases for selective C‐methylation of linear terpenoids. The engineered enzyme catalyzes selective methylation of unactivated alkenes in mono‐, sesqui‐ and diterpenoids to produce C11, C16 and C21 derivatives. Preparative conversion and product isolation reveals that this biocatalyst performs C−C bond formation with high chemo‐ and regioselectivity. The alkene methylation most likely proceeds via a carbocation intermediate and regioselective deprotonation. This method opens new avenues for modifying the carbon scaffold of alkenes in general and terpenoids in particular.
Terpenoids are applied in various ways, in flavors and fragrances as well as in pharmaceuticals and plant protection. Through diversification of the carbon scaffold, non‐natural terpenoids can be generated and screened for improved properties. The identification and engineering of methyltransferases for late‐stage C‐methylation of unactivated alkenes with high selectivity provided access to methylated derivatives of readily available terpenoids.
Developmental programming refers to the long-term programming of gene expression during fetal and postnatal development, resulting in altered organ function even into adulthood. This review describes ...how maternal and paternal sustenance and stress, as well as fetal sex, all matter in large animal models and affect developmental programming of the offspring.
Developmental programming is the concept that certain health outcomes throughout life can be linked to early fetal or postnatal development. Progress in understanding concepts and mechanisms surrounding developmental programming is heavily leveraged by the use of large animal models. Numerous large animal models have been developed that apply a host of different maternal stressors and, more recently, paternal stressors. Maternal nutrition is the most researched maternal stressor applied during gestation and includes both global nutrient supply and models that target specific macro- or micro- nutrients. The focus of this review is to provide an overview of the many large animal models of developmental programming and to discuss the importance of sex effects (including paternal contributions) in study design and data interpretation.
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