The Wittig-typec arbonyl olefination reactionhas no biocatalytic equivalent. To build complex molecular scaffolds, however, CÀCb ond-formingr eactions are pivotal for biobased economy and synthetic biology. The heme-containing E. coli protein YfeX was found to catalyzec arbonyl olefination by reactiono fb enzaldehydew ith ethyl diazoacetateu nder aerobic conditions in the absence of at riphenylphosphine oxophile. The reaction was performed in whole cells and showed ap roduct formation of 440 mg L À1 in 1h.I tw as, moreover,s hown that the reaction could be performed under Wittig-analogue conditions in the presenceo ft riphenylphosphine or triphenylarsine.Although several chemical methods forC ÀCb ond formation are known, biocatalytic alternatives are less developed. Amongst the most established methods are the Grignardr eaction, [1] hydroformylation, [2] andt he Wittig reaction.[3] Ab reakthrough in metal-catalyzed CÀCb ond formation was achieved by the cross-coupling chemistry of Heck, [4] Negishi, [5] and Suzuki, [6] which,t oday,a re standard methods in chemistry laboratories.To construct molecular scaffolds by biocatalytic means, alternative CÀCb ond-forming enzymes are required. Amongst the CÀCb ond-forminge nzymes are aldolases, [7] cyanohydrin lyases, [8] thiamin diphosphate dependent lyases, [9] methyltransferases, [10] and cyclases. [11] We recently reported the catalysis of Friedel-Crafts-type [12] and Prins-ene-typer eactions [11] by am utated squalene-hopenec yclase. The substrate scope, however, of the lyases was very limited, andc yclases have thus far only been shown to catalyze intramolecular reactions.CÀCb ondf ormation reactions are particularly important in synthetic biology,f or which artificial reaction pathways are genetically engineered into organisms and used for the production of industrially relevant molecules.[13] Arnold and co-workers impressively showed the use of heme-containing P450s-which naturally catalyzeh ydroxylation reactions [14,15] -to catalyze carbenoid insertion into C=C [16] and NÀHb onds (Scheme 1).[17] Fasan et al. accomplished these reactions [18,19] and SÀHi nsertions [20] with sperm-whale myoglobin. All these reactions relied on electrophilicc arbenes.Apromising strategyfor the development of novel enzymatic reactions is through analysisofthe transition states of chemical reactions of interest and by comparing these transition states to those existing in biocatalytic reactions. We focused on reactions with nucleophilic carbon atoms,a st hey are required to perform CÀCb ond-forming reactions. The in situ formed iron carbenoid species in the abovementioned hemecatalyzed reactions assembles into as tructure similart ot hat of aC =Pp hosphorane. The carbon atom of these phosphoranes is used in Wittig-type reactions for nucleophilic attack at carbonyl groups and in this way performs carbonyl olefinations.Another example of at ransition state similar to the iron carbenoid species is that formed in the Büchner-Curtius-Schlotterbeck reaction. [21,22] AC ÀCb ond is formed by ...

The reduction of activated C=C double bonds is an important reaction in synthetic chemistry owing to the potential formation of up to two new stereogenic centers. Artificial nicotinamide cofactors were recently presented as alternative suppliers of hydride equivalents needed for alkene reduction. To study the effect of cofactors on the reduction of activated alkenes, a set of N‐substituted synthetic nicotinamide cofactors with differing oxidation potentials were synthesized and their electrochemical and kinetic behavior was studied. The effects of the synthetic cofactors on enzyme activity of four ene reductases are outlined in this study, where the cofactor mimic with an N‐substituted 4‐hydroxy‐phenyl residue led to a sixfold higher vmax relative to the natural cofactor NADH.

The facile synthesis of rifamycin S from rifamycin B, a member of the ansamycin family of antibiotics, via the oxidation of rifamycin B was developed. Currently on an industrial scale, this oxidation is performed using harsh pH conditions and chlorinated solvents. With the development of a suitable buffer/ methanol system, a similar yield and space-time-yield in comparison to the current process can be obtained renouncing chlorinated solvents. Employment of methanol as a reaction medium in this process is crucial for attaining high yields under mild reaction conditions. With this method a space-time-yield of 189 g L −1 h −1 of rifamycin S was achieved in one step.

The Cover shows an enzymatic carbonyl olefination reaction in E.coli where the corresponding enzyme—depicted as the clownfish nemo—has to be found in the organism which is represented by the ocean. In their paper, Weissenborn, Löw et al. present a method to find new enzyme activities by utilizing an entire cell lysate with its thousands of proteins as catalyst. Once they found that the cell lysate catalyzes a carbonyl olefination reaction they determined, isolated, and studied the corresponding protein. The results show the first enzymatic carbonyl olefination in absence of phosphines, as well as the feasibility of the performed general approach in cell lysates. More information can be found in the Communication by Weissenborn, Löw et al. on page 1636 in Issue 9, 2016 (DOI: 10.1002/cctc.201600227).

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