Volume 17 Issue 1, January 2021

Bariatric surgery causes high rates of remission of type 2 diabetes; however, the mechanisms remain unresolved. A new study identifies cholic-acid-7-sulfate as a novel contributor to the metabolic benefits of bariatric surgery and an attractive target for treatment of type 2 diabetes.

Reprogramming requires resetting the epigenome toward a pluripotent chromatin state. A new chemical screen identifies epigenetic and signaling roadblocks for reprogramming of human somatic cells, with the inhibition of these roadblocks resulting in a more permissive epigenome for reprogramming.

Metabolic engineering offers the flexibility to meet market demand for bioactive natural products but can be hampered when a necessary protein or intermediate is toxic. In yeast, modifying the subcellular localization of biosynthetic enzymes can alleviate toxicity and increase production titer.

This Review summarizes recent advances in CRISPR–Cas regulation mechanisms by natural biomolecules that enhance or inhibit CRIPSR–Cas immunity, as well as their applications in CRISPR biology and technologies.

Levels of the endogenous bile acid cholic acid-7-sulfate (CA7S) increase in the gastrointestinal tract of both mice and humans after sleeve gastrectomy. CA7S acts through the G-protein-coupled receptor TGR5 to increase glucose tolerance during insulin resistance.

The fluorescent chemogenetic reporters greenFAST and redFAST were engineered by protein engineering. They display orthogonal fluorogen recognition and spectral properties allowing efficient multicolor imaging of proteins in live cells and organisms.

A fluorescence-based sensor of PKA activity has increased brightness, dynamic range and signal-to-noise ratio over related sensors and is useful for visualizing kinase activity in HeLa cells, primary neurons and the cortex of awake mice.

A chemical screen targeting major epigenetic pathways identifies permissive epigenetic states that enable reprogramming with a broad range of transcriptional regulators and almost all octamer-binding (OCT) family members.

Structural analysis of transcription activation complex comprising E. coli transcription factor CueR, RNAP holoenzyme and promoter DNA reveals that CueR distorts the DNA conformation to promote the association of promoter with polymerase.

Structural and kinetic analyses of the transcriptional repressor SqrR in multiple states indicate that its persulfide selectivity is determined by structural frustration in the disulfide form, favoring formation of the tetrasulfide-bridged product.

Reengineering of the lac operon in E. coli from a ligand-inducible to a blue-light-regulated gene expression system facilitates optogenetic control of biotechnological applications including metabolic engineering and protein expression.

The authors identified a pH-dependent protonated status in the miR-21 precursor, which leads to additional base pairing in its secondary structure, thus affecting Dicer processing and miR-21 maturation.

Native ion mobility mass spectrometry reveals two isoforms of the two-pore domain K⁺ channel K2P4.1 have distinct binding preferences for lipids and show a relationship between the strength of individual lipid binding events and channel activity.

Increased production of (S)-reticuline and other alkaloids is achieved through alleviating norcoclaurine synthase toxicity by targeting the enzyme to the peroxisome plus enlarging peroxisomes by expression of engineered transcription factors.

A two-cell setup containing tryptophanase, a flavin-dependent monooxygenase and a regiospecific halogenase (linked to a flavin reductase as a solubility tag) enables the production of 6,6'-dibromoindigo and other indigoid dyes in Escherichia coli.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.