Lombardi, A.; Nastri, F.

Int. J. Mol. Sci. 2018, 19, 2896, 10.3390/ijms19102896

Many efforts are continuously devoted to the construction of hybrid biomaterials for specific applications, by immobilizing enzymes on different types of surfaces and/or nanomaterials. In addition, advances in computational, molecular and structural biology have led to a variety of strategies for designing and engineering artificial enzymes with defined catalytic properties. Here, we report the conjugation of an artificial heme enzyme (MIMO) with lipoic acid (LA) as a building block for the development of gold-based biomaterials. We show that the artificial MIMO@LA can be successfully conjugated to gold nanoparticles or immobilized onto gold electrode surfaces, displaying quasi-reversible redox properties and peroxidase activity. The results of this work open interesting perspectives toward the development of new totally-synthetic catalytic biomaterials for application in biotechnology and biomedicine, expanding the range of the biomolecular component aside from traditional native enzymes.

Arseniyadis, S.; Campagne, J.; Smietana, M.

Chem. Eur. J. 2020, 26, 3519-3523, 10.1002/chem.202000516

While artificial cyclases hold great promise in chemical synthesis, this work presents the first example of a DNA-catalyzed inverse electron-demand hetero-Diels–Alder (IEDHDA) between dihydrofuran and various α,β-unsaturated acyl imidazoles. The resulting fused bicyclic O,O-acetals containing three contiguous stereogenic centers are obtained in high yields (up to 99 %) and excellent diastereo- (up to >99:1 dr) and enantioselectivities (up to 95 % ee) using a low catalyst loading. Most importantly, these results show that the concept of DNA-based asymmetric catalysis can be expanded to new synthetic transformations offering an efficient, sustainable, and highly selective tool for the construction of chiral building blocks.

Lombardi, A.; Maglio, O.; Nastri, F.

Biopolymers 2018, 109, e23107, 10.1002/bip.23107

Inspired by natural heme‐proteins, scientists have attempted for decades to design efficient and selective metalloporphyrin‐based oxidation catalysts. Starting from the pioneering work on small molecule mimics in the late 1970s, we have assisted to a tremendous progress in designing cages of different nature and complexity, able to accommodate metalloporphyrins. With the intent of tuning and controlling their reactivity, more and more sophisticated and diverse environments are continuously exploited. In this review, we will survey the current state of art in oxidation catalysis using iron‐ and manganese‐porphyrins housed within designed or engineered protein cages. We will also examine the innovative metal‐organic framework (MOF) systems, exploited to achieving an enzyme‐like environment around the metalloporphyrin cofactor.

Matsuo, T.

Chem. - Asian J. 2011, 6, 2491-2499, 10.1002/asia.201100107

H64D myoglobin mutant was reconstituted with two different types of synthetic hemes that have aromatic rings and a carboxylate‐based cluster attached to the terminus of one or both of the heme‐propionate moieties, thereby forming a “single‐winged cofactor” and “double‐winged cofactor,” respectively. The reconstituted mutant myoglobins have smaller Km values with respect to 2‐methoxyphenol oxidation activity relative to the parent mutant with native heme. This suggests that the attached moiety functions as a substrate‐binding domain. However, the kcat value of the mutant myoglobin with the double‐winged cofactor is much lower than that of the mutant with the native heme. In contrast, the mutant reconstituted with the single‐winged cofactor has a larger kcat value, thereby resulting in overall catalytic activity that is essentially equivalent to that of the native horseradish peroxidase. Enhanced peroxygenase activity was also observed for the mutant myoglobin with the single‐winged cofactor, thus indicating that introduction of an artificial substrate‐binding domain at only one of the heme propionates in the H64D mutant is the optimal engineering strategy for improving the peroxidase activity of myoglobin.

Matsuo, T.

Tetrahedron Lett. 2019, 60, 151226, 10.1016/j.tetlet.2019.151226

Organic synthesis using biocatalysts has been developed over many years and is still a prominent area of research. In this context, various hybrid biocatalysts composed of a synthetic metal complex catalyst and a protein scaffold (i.e. artificial metalloenzymes) have been constructed. One of the most recent research areas in biocatalysts-mediated synthesis is CC bond/cleavage, the most important type of reaction in organic chemistry. Some of the artificial enzymes were applied to in-cell reactions as well as in vitro systems. The effects of the structural fluctuation in biomacromolecules on their functions have also been realized. This review article includes recent research examples of artificial metalloenzymes used to CC bond formation/cleavage. As a perspective, we also focus on how we apply protein dynamics factor for the creation of new generation artificial metalloenzymes.