Protein engineering articles from across Nature Portfolio

Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.

Conventional blue denim dyeing has both environmental and health-related consequences. Here, Bidart et al. use enzyme engineering to develop a viable method for the bulk production of indican and demonstrate dying processes which could significantly reduce the negative consequences of this billion-dollar industry.

Existing TadA-derived CBEs exhibit residual A•T-to-G•C editing activity and suffer from lower activity at several sequence contexts and with non-SpCas9 targeting domains. Here, the authors use phage-assisted evolution to evolve CBE6 variants that address these limitations.

In contrast to their clinical success as inhibitors and targeting agents, antibodies have generally been ineffective as receptor agonists. Here, Romei et al. leverage a natural homotypic interface to tune antibody geometry, enabling optimization of agonist activity for multiple therapeutic targets.

Plant alkaloids – an important class of pharmaceuticals - are still largely acquired through phytoextraction. Here, the authors develop an artificial and concise four-enzyme biocatalytic cascade for synthesizing various phenethylisoquinoline alkaloids from readily available starting materials.

Enantioselective γ-lactonization of unactivated C(sp³)–H bonds is a challenge using chemical methods. Now the biocatalytic enantioselective synthesis of γ-lactones from aliphatic carboxylic acids is reported, using a reengineered fatty acid hydroxylase, P450_BSβ. Crystallographic and computational analyses show the observed γ-regioselectivity arises from the mutants introduced into P450_BSβ.

Antigen–antibody prediction remains a complex computational challenge. Simulations with the new Absolut! package provide novel insights into the models and datasets tackling this problem.

The 2018 Nobel prizes in chemistry and medicine celebrate tools for engineering biological materials.