Significance: Metal homeostasis is an integral part of metabolism for any organism. A vast array of natural products are already known to mediate iron homeostasis in fungi and bacteria; however, unlike their bacterial counterparts, to date, there are no known fungal small molecules that function to maintain copper homeostasis. Discovery of copper-binding xanthocillins produced by Aspergillus fumigatus gives insight into mechanisms other than the extensively studied copper transporters or metalloproteins for how fungi can regulate copper. This has important ecological implications, as securing scarce nutrients is central for fitness and survival. Conservation of the xanthocillin biosynthetic machinery across filamentous fungal taxa offers a new paradigm in eukaryotic metal homeostasis.

In this contribution, we report chemoenzymatic bromodecarboxylation (Hunsdiecker-type) of α,ß-unsaturated carboxylic acids. The extraordinarily robust chloroperoxidase from Curvularia inaequalis (CiVCPO) generated hypobromite from H₂O₂ and bromide, which then spontaneously reacted with a broad range of unsaturated carboxylic acids and yielded the corresponding vinyl bromide products. Selectivity issues arising from the (here undesired) addition of water to the intermediate bromonium ion could be solved by reaction medium engineering. The vinyl bromides so obtained could be used as starting materials for a range of cross-coupling and pericyclic reactions.

In this study, engineered imine reductases (IREDs) of IRED M5, originally fromActinoalloteichus hymeniacidonis, were obtained through structure-guided semi-rational design.

Chiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase from Rhodococcus erythropolis. This enzyme normally catalyzes hydrolysis with formation of vicinal diols. Firstly, the required shutdown of the undesired natural water-mediated ring-opening is achieved by rational mutagenesis of the active site. In silico enzyme design is then continued with generation of the improved mutants. These variants prove to be versatile catalysts for preparing chiral N- and O-heterocycles with up to 99% conversion, and enantiomeric ratios up to 99:1. Crystal structural data and computational modeling reveal that Baldwin-type cyclizations, catalyzed by the reprogrammed enzyme, are enabled by reshaping the active-site environment that directs the distal RHN and HO-substituents to be intramolecular nucleophiles.