Biocatalysis enables the scalable conversion of biobased furans into various furfurylamines.

Biobased furans have emerged as chemical building blocks for the development of materials because of their diverse scaffolds and as they can be directly prepared from sugars. However, selective, efficient, and cost-effective scalable conversion of biobased furans remains elusive. Here, we report a robust transaminase (TA) from Shimia marina (SMTA) that enables the scalable amination of biobased furanaldehydes with high activity and broad substrate specificity. Crystallographic and mutagenesis analyses provide mechanistic insights and a structural basis for understanding SMTA, which enables a higher substrate conversion. The enzymatic cascade process established in this study allows one-pot synthesis of 2,5-bis(aminomethyl)furan (BAMF) and 5-(aminomethyl)furan-2-carboxylic acid from 5-hydroxymethylfurfural. The biosynthesis of various furfurylamines, including a one-pot cascade reaction for BAMF generation using whole cells, demonstrates their practical application in the pharmaceutical and polymer industries.

The High-Resolution Structure Reveals Remarkable Similarity in PD-1 Binding of Cemiplimab and Dostarlimab, the FDA-Approved Antibodies for Cancer Immunotherapy.

Multiple tumors have responded well to immunotherapies, which use monoclonal antibodies to block the immune checkpoint proteins and reactivate the T-cell immune response to cancer cells. Significantly, the anti-PD-1 antibodies pembrolizumab and nivolumab, which were approved in 2014, have revolutionized cancer therapy, demonstrating dramatic improvement and longer duration. The US FDA authorized the third anti-PD-1 medication, cemiplimab, in 2018 for use in patients with cutaneous squamous cell carcinoma. To further understand the molecular mechanism of the antibody drug, we now reveal the intricate structure of PD-1 in complex with the cemiplimab Fab at a resolution of 1.98 Å. The cemiplimab-PD-1 interaction preoccupies the space for PD-L1 binding with a greater binding affinity than the PD-1/PD-L1 interaction, which is the basis for the PD-1 blocking mechanism. The structure reveals that cemiplimab and dostarlimab are significantly similar in PD-1 binding, although the precise interactions differ. A comparative investigation of PD-1 interactions with the four FDA-approved antibodies reveals that the BC, C'D, and FG loops of PD-1 adopt distinct conformations for optimal interaction with the antibodies. The structural characteristics in this work could be helpful information for developing more potent anti-PD-1 biologics against cancer.