Biocatalysis employing imine reductases is ap romising approach for the one-step generation of chiral amines from ketones. The enzymes reported for this process suffer from low activity and moderate stereoselectivity.W ei dentified as et of enzymest hat facilitate this reaction with high to quantitative conversionsf rom al ibrary of 28 imine reductases. This enabled the conversion of ketones with ammonia, methylamine, or butylamine into the corresponding amines. Most importantly,w e performed preparative (> 100 mg) scale syntheses of amines such as (1S,3R)-N,3-dimethylcyclohexylamine and (R)-N-methyl-2-aminohexane with excellent stereochemical purities (98 % de, 96 % ee)i ng ood yields.Chiral amines are keys tructuralm otifs that are frequently employedf or the preparation of pharmacologically active compounds.[1] From av ariety of asymmetric synthesis methods, transition-metal-catalyzed reductionso fi mine or enamine precursors [2] dominate the spectrum of approaches that have been reported.[3] However,t hese reactions equences usually comprise severals teps, including protection and deprotection of the amine and the necessity to introduce nitrogen activating groups for the reduction (Scheme 1, routes Aand B). [2] Biocatalysis offers an attractive alternative for synthetic chemists, with ac ontinuouslyi ncreasing toolboxo fe nzymes for the preparation of chiral amines. [1b, 4] Amine transaminases [1b, 5] and amine dehydrogenases, [6] for example, have proven to be applicable in the one-step preparation of primary amines,a lso on industrial scale. [5c, 7] Thus, these enzymes can providea na ttractive synthetic shortcut towards chiral amines. Additionally,C odexis lately filed ap atento ne ngineered opine dehydrogenases that catalyze reductive aminations.[8] NADPHdependenti mine reductases (IREDs) also catalyze the equivalent single-step reduction (Scheme 1, route C) but are, unlike amine transaminases anda mine dehydrogenases, not limited to the preparation of primary amines. IREDs are amenable to access primary,secondary,and tertiary amines starting from ketones or the respective imine or iminium ion. Whereas imine reductionsh ave been knownf or some time to occur in several metabolic pathways such as dihydrofolate, opine, opioid, and antibiotic synthesis, [9] it was only over the last five years that NADPH-dependentI REDs were reported in the context of synthetic applications.[10] Immediately after the isolation of the first amino acid sequences, [10] several research groups thoroughly studied IREDs for the reduction of variousc yclic imines and iminium ion substrates, also including artificial metal-dependentI REDs.[11] Very recently,t he group of Müllerr eported the first IRED-catalyzed reductivea mination of ak etone with methylamine in ap roofo fp rinciple study.[11e] With this work, he paved the way for an ew synthetic application of IREDs. Nestl and co-workersd emonstrated that IRED-catalyzedr eductive amination is, in principle, applicable for different amines, which thuso pened the gate for the sy...

Imine reductases (IREDs) show great potential as catalysts for reductive amination of ketones to produce chiral secondary amines.

Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene‐sequence‐similarity‐based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non‐ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.

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