Nicholas J. Turner

Modeling the Antecedents of Proactive Behavior at Work

Using a sample of U.K. wire makers (N = 282), the authors tested a model in which personality and work environment antecedents affect proactive work behavior via cognitive-motivational mechanisms. Self-reported proactive work behaviors (proactive idea implementation and proactive problem solving) were validated against rater assessments for a subsample (n = 60) of wire makers. With the exception of supportive supervision, each antecedent was important, albeit through different processes. Proactive personality was significantly associated with proactive work behavior via role breadth self-efficacy and flexible role orientation, job autonomy was also linked to proactive behavior via these processes, as well as directly; and coworker trust was associated with proactive behavior via flexible role orientation. In further support of the model, the cognitive-motivational processes for proactive work behavior differed from those for the more passive outcome of generalized compliance.

Directed evolution drives the next generation of biocatalysts

Enzymes are increasingly being used as biocatalysts in the generation of products that have until now been derived using traditional chemical processes. Such products range from pharmaceutical and agrochemical building blocks to fine and bulk chemicals and, more recently, components of biofuels. For a biocatalyst to be effective in an industrial process, it must be subjected to improvement and optimization, and in this respect the directed evolution of enzymes has emerged as a powerful enabling technology. Directed evolution involves repeated rounds of (i) random gene library generation, (ii) expression of genes in a suitable host and (iii) screening of libraries of variant enzymes for the property of interest. Both in vitro screening-based methods and in vivo selection-based methods have been applied to the evolution of enzyme function and properties. Significant developments have occurred recently, particularly with respect to library design, screening methodology, applications in synthetic transformations and strategies for the generation of new enzyme function.

Transformational Leadership and Psychological Well-Being: The Mediating Role of Meaningful Work

Two studies investigated the relationship between transformational leadership, the meaning that individuals ascribe to their work, and their psychological well-being. In Study 1, the perceptions of meaningful work partially mediated the relationship between transformational leadership and positive affective well-being in a sample of Canadian health care workers (N=319). In Study 2, the meaning that a separate sample of service workers (N=146) ascribed to their work fully mediated the relationship between transformational leadership and psychological well-being, after controlling for humanistic work beliefs. Overall, these results support and add to the range of positive mental health effects associated with transformational leadership and are suggestive of interventions that organizations can make to improve well-being of workers.

Predicting workplace aggression: a meta-analysis.

The authors conducted a meta-analysis of 57 empirical studies (59 samples) concerning enacted workplace aggression to answer 3 research questions. First, what are the individual and situational predictors of interpersonal and organizational aggression? Second, within interpersonal aggression, are there different predictors of supervisor- and coworker-targeted aggression? Third, what are the relative contributions of individual (i.e., trait anger, negative affectivity, and biological sex) and situational (i.e., injustice, job dissatisfaction, interpersonal conflict, situational constraints, and poor leadership) factors in explaining interpersonal and organizational aggression? Results show that both individual and situational factors predict aggression and that the pattern of predictors is target specific. Implications for future research are discussed.

Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes

Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d6-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction. An artificial transfer hydrogenase, based on the incorporation of a biotinylated iridium-piano-stool complex in streptavidin, is shown to be fully compatible with a range of biocatalysts. The location of the active metal centre inside the protein scaffold efficiently prevents mutual inactivation processes and enables the concurrent interplay with oxidative enzymes.

Carboxylic acid reductase is a versatile enzyme for the conversion of fatty acids into fuels and chemical commodities.

Aliphatic hydrocarbons such as fatty alcohols and petroleum-derived alkanes have numerous applications in the chemical industry. In recent years, the renewable synthesis of aliphatic hydrocarbons has been made possible by engineering microbes to overaccumulate fatty acids. However, to generate end products with the desired physicochemical properties (e.g., fatty aldehydes, alkanes, and alcohols), further conversion of the fatty acid is necessary. A carboxylic acid reductase (CAR) from Mycobacterium marinum was found to convert a wide range of aliphatic fatty acids (C6–C18) into corresponding aldehydes. Together with the broad-substrate specificity of an aldehyde reductase or an aldehyde decarbonylase, the catalytic conversion of fatty acids to fatty alcohols (C8–C16) or fatty alkanes (C7–C15) was reconstituted in vitro. This concept was applied in vivo, in combination with a chain-length-specific thioesterase, to engineer Escherichia coli BL21(DE3) strains that were capable of synthesizing fatty alcohols and alkanes. A fatty alcohol titer exceeding 350 mg·L−1 was obtained in minimal media supplemented with glucose. Moreover, by combining the CAR-dependent pathway with an exogenous fatty acid-generating lipase, natural oils (coconut oil, palm oil, and algal oil bodies) were enzymatically converted into fatty alcohols across a broad chain-length range (C8–C18). Together with complementing enzymes, the broad substrate specificity and kinetic characteristics of CAR opens the road for direct and tailored enzyme-catalyzed conversion of lipids into user-ready chemical commodities.

Cytochromes P450 as useful biocatalysts: addressing the limitations

Cytochrome P450 monooxygenases (P450s or CYPs) are a unique family of enzymes which are capable of catalysing the regio- and stereospecific oxidation of non-functionalised hydrocarbons. Despite the enormous synthetic potential of P450s, these enzymes have yet to be extensively employed for research purposes or in industry. Lack of stability, low activity, narrow substrate specificity, expensive cofactor requirements, limited solvent tolerance and electron supply are some of the main reasons why the academic and industrial implementation of these important biocatalysts remains a challenge. Considering the significance of P450s, many research groups have focused on improving their properties in an effort to make more robust catalysts with broad synthetic applications. This article focuses on some of the factors that have limited the exploitation of P450s and explores some of the significant steps that have been taken towards addressing these limitations.

Enantioselective Biocatalytic Oxidative Desymmetrization of Substituted Pyrrolidines

Direct activation of sp C H bonds a to a nitrogen atom represents an attractive strategy for functionalization of amines, especially those found in 5and 6-membered ring heterocycles. In particular, C H activation by oxidation, followed by nucleophilic addition, generates products of an overall oxidative Strecker or Mannich process. Recent reports have described the use of various metal-based oxidants to achieve this transformation although there are few examples of catalytic and/or enantioselective processes. The enantioselective oxidation of N-protected pyrrolidines has been reported using manganese–salen catalysts and iodosobenzene as the stoichiometric oxidant. Herein we report the enantioselective enzyme-catalyzed desymmetrization of a range of unprotected pyrrolidines to the corresponding Dpyrrolines (Scheme 1), which serve as useful building blocks for the synthesis of l-proline analogues of high enantiomeric purity.

Identification of a new class of cytochrome P450 from a Rhodococcus sp.

A degenerate set of PCR primers were used to clone a gene encoding a cytochrome P450 (the P450RhF gene) from Rhodococcus sp. strain NCIMB 9784 which is of unique primary structural organization. Surprisingly, analysis of the translation product revealed that the P450 is fused to a reductase domain at the C terminus which displays sequence conservation for dioxygenase reductase proteins. The reductase partner comprises flavin mononucleotide- and NADH-binding motifs and a [2Fe2S] ferredoxin-like center. The gene was engineered for heterologous expression in Escherichia coli, and conditions were found in which the enzyme was produced in a soluble form. A recombinant strain of E. coli was able to mediate the O dealkylation of 7-ethoxycoumarin in good yield, despite the absence of any recombinant redox proteins. This unprecedented finding leads us to propose that P450RhF represents the first example of a new class of cytochromes P450 in which the reducing equivalents are supplied by a novel reductase in a fused arrangement.

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

A clean and green approach to amines Enzymes evolved to operate in water and to modify their substrates using comparatively nontoxic reagents. Thus, a major advantage of applying enzymes to synthetic chemistry is their compatibility with environmentally benign conditions. Mutti et al. report that two enzymes—alcohol and amine dehydrogenases—can operate in tandem to convert alcohols to amines. The reaction proceeds with ammonium as the only input and water as the only byproduct. The mechanism relies on consecutive oxidation and reduction steps, with hydrogen shuttled by a nicotinamide coenzyme. Science, this issue p. 1525 The pairing of two enzymes offers an environmentally benign protocol for the conversion of alcohols to amines. α-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale. We present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on a combination of two enzymes: an alcohol dehydrogenase (from Aromatoleum sp., Lactobacillus sp., or Bacillus sp.) operating in tandem with an amine dehydrogenase (engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols, yielding up to 96% conversion and 99% enantiomeric excess. Primary alcohols were aminated with high conversion (up to 99%). This redox self-sufficient cascade possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product.