Despite major recent advances in C–H activation, discrimination between two similar, unactivated C–H positions is beyond the scope of current chemocatalytic methods. Here we demonstrate that integration of regioselective halogenase enzymes with Pd-catalysed cross-coupling chemistry, in one-pot reactions, successfully addresses this problem for the indole heterocycle. The resultant ‘chemobio-transformation' delivers a range of functionally diverse arylated products that are impossible to access using separate enzymatic or chemocatalytic C–H activation, under mild, aqueous conditions. This use of different biocatalysts to select different C–H positions contrasts with the prevailing substrate-control approach to the area, and presents opportunities for new pathways in C–H activation chemistry. The issues of enzyme and transition metal compatibility are overcome through membrane compartmentalization, with the optimized process requiring no intermediate work-up or purification steps.
Flavin‐dependent halogenases are useful enzymes for providing halogenated molecules with improved biological activity, or intermediates for synthetic derivatization. We demonstrate how the fungal halogenase RadH can be used to regioselectively halogenate a range of bioactive aromatic scaffolds. Site‐directed mutagenesis of RadH was used to identify catalytic residues and provide insight into the mechanism of fungal halogenases. A high‐throughput fluorescence screen was also developed, which enabled a RadH mutant to be evolved with improved properties. Finally we demonstrate how biosynthetic genes from fungi, bacteria, and plants can be combined to encode a new pathway to generate a novel chlorinated coumarin “non‐natural” product in E. coli.
Guided by self-determination theory, the present study examines independent and interactive roles of self-efficacy and perceived social support in predicting types of academic motivation. Data were collected from 325 university undergraduates in 18-23 years of age (M=21.09, SD=1.34) from the fifth biggest city of South Asia. Results showed the independent and interactive effects of self-efficacy and social support from friends and from a significant other on intrinsic academic motivation after controlling the potential confounding due to demographics. Social support from friends, but not from family and a significant other, independently predicted extrinsic academic motivation. Neither self-efficacy nor social support significantly predicted amotivation.
Flavin-dependent halogenases are useful enzymes for providing halogenated molecules with improved biological activity,o ri ntermediates for synthetic derivatization. We demonstrate how the fungal halogenase RadH can be used to regioselectively halogenate ar ange of bioactive aromatic scaffolds.S ite-directed mutagenesis of RadH was used to identify catalytic residues and provide insight into the mechanism of fungal halogenases.Ahigh-throughput fluorescence screen was also developed, whichenabled aRadH mutant to be evolved with improved properties.Finally we demonstrate how biosynthetic genes from fungi, bacteria, and plants can be combined to encode an ew pathwayt og enerate an ovel chlorinated coumarin "non-natural" product in E. coli.
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