Artificial Small Molecules as Cofactors and Biomacromolecular Building Blocks in Synthetic Biology: Design, Synthesis, Applications, and Challenges

Abstract

Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial small molecules have been successfully used in enzyme engineering. The types of enzymatic reactions and metabolic pathways in cells can be expanded by the incorporation of these artificial small molecules either as cofactors or as building blocks of proteins and nucleic acids, which greatly promotes the development and application of biotechnology. In this review, we summarized research on artificial small molecules including biological metal cluster mimics, coenzyme analogs (mNADs), designer cofactors, non-natural nucleotides (XNAs), and non-natural amino acids (nnAAs), focusing on their design, synthesis, and applications as well as the current challenges in synthetic biology.

Unnatural Amino Acids for Biological Spectroscopy and Microscopy

“…UAAs have found a wide range of utility in biological science. − However, in order for a UAA to be useful as a spectroscopic and/or imaging reporter of proteins, it must meet several requirements: (1) it should be able to produce a detectable, distinguishable, and interpretable signal (e.g., a vibrational or fluorescence signal) with desired spectroscopic properties; (2) it should be a simple derivative of one of the canonical amino acids; (3) it should be chemically stable; (4) it should not significantly perturb the structural and functional properties of the protein in question; and (5) it should be able to be incorporated into proteins via either a chemical or biological method.…”