Redirecting the JAK-STAT signal blocks the SARS-CoV-2 replication.

The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-ß, a phase II clinical cytokine with 3-amino tyrosine (IFN-ß-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-ß-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection.

Building biomaterials through genetic code expansion.

Genetic code expansion (GCE) enables directed incorporation of noncoded amino acids (NCAAs) and unnatural amino acids (UNAAs) into the active core that confers dedicated structure and function to engineered proteins. Many protein biomaterials are tandem repeats that intrinsically include NCAAs generated through post-translational modifications (PTMs) to execute assigned functions. Conventional genetic engineering approaches using prokaryotic systems have limited ability to biosynthesize functionally active biomaterials with NCAAs/UNAAs. Codon suppression and reassignment introduce NCAAs/UNAAs globally, allowing engineered proteins to be redesigned to mimic natural matrix-cell interactions for tissue engineering. Expanding the genetic code enables the engineering of biomaterials with catechols - growth factor mimetics that modulate cell-matrix interactions - thereby facilitating tissue-specific expression of genes and proteins. This method of protein engineering shows promise in achieving tissue-informed, tissue-compliant tunable biomaterials.

Esterification of Polymeric Carbohydrate Through Congener Cutinase-Like Biocatalyst.

Cutinase-like enzymes (CLEs) are bi-functional hydrolases, which share the conserved catalytic site of lipase and consensus pentapeptide sequence of cutinase. Here, we have genetically replaced the canonical amino acids (CAA) by their non-canonical fluorinated surrogates to biosynthesize a novel class of congener biocatalyst for esterification of polymeric carbohydrate with long-chain fatty acid. It is a new enzyme-engineering approach used to manipulate industrially relevant biocatalyst through genetic incorporation of new functionally encoded non-canonical amino acids (NCAA). Global fluorination of CLE improved its catalytic, functional, and structural stability. Molecular docking studies confirmed that the fluorinated CLE (FCLE) had developed a binding affinity towards different fatty acids compared with the parent CLE. Importantly, FCLE could catalyze starch oleate synthesis in 24 h with a degree of substitution of 0.3 ± 0.001. Biophysical and microscopic analysis substantiated the efficient synthesis of the ester by FCLE. Our data represent the first step in the generation of an industrially relevant fluorous multifunctional enzyme for facile synthesis of high fatty acid starch esters.