Engineered P450 enzymes constitute attractive catalysts for the selective oxidation of unactivated C-H bonds in complex molecules. A current bottleneck in the use of P450 catalysis for chemical synthesis is the time and effort required to identify the P450 variant(s) with the desired level of activity and selectivity. In this report, we describe a method to map the active site configuration of engineered P450 variants in high throughput using a set of semisynthetic chromogenic probes. Through analysis of the resulting 'fingerprints', reliable predictions can be made regarding the reactivity of these enzymes toward complex substrates structurally related to the fingerprint probes. In addition, fingerprint analysis offers a convenient and time-effective means to assess the regioselectivity properties of the fingerprinted P450s. The described approach can represent a valuable tool to expedite the discovery of P450 oxidation catalysts for the functionalization of relevant natural products such as members of the terpene family.
The transition from adolescence to young adulthood is a dynamic developmental period during which youth are striving for social independence while simultaneously undergoing maturation of cognitive control skills. Variation in growth trajectories of adolescent neurocognitive development has been hypothesized to contribute to adverse outcomes in the transition to adulthood, such as experiencing violence. However, there remains a lack of consensus on the normative trajectory of cognitive maturation. To address this problem, we derive a Cognitive Maturity Index (CMI), to estimate the difference between chronological and cognitive age predicted with latent factor estimates of inhibitory control, risky decision-making and emotional processing measured with standard neuropsychological instruments. Age prediction with latent factor estimates of cognitive skills approximated age within 10 months (Pearson's Correlation r=0.71). Males in advanced puberty displayed lower cognitive maturity relative to peers of the same age; manifesting as weaker inhibitory control, greater risk taking, desensitization to negative affect, and poor recognition of positive affect. Elevated risk for future violent outcomes was effected by delayed CMI and fully mediated by drive for achieving rewards, illustrating adolescent maturation as a risk traversal process into young adulthood. This work provides a foundation for deriving a more precise definition of cognitive maturity to aid empirical assessment of individual-specific developmental risk factors for adverse outcomes in emerging adulthood.
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