Tanaka, K.

Nat. Catal. 2019, 2, 780-792, 10.1038/s41929-019-0317-4

The ability of natural metalloproteins to prevent inactivation of their metal cofactors by biological metabolites, such as glutathione, is an area that has been largely ignored in the field of artificial metalloenzyme (ArM) development. Yet, for ArM research to transition into future therapeutic applications, biocompatibility remains a crucial component. The work presented here shows the creation of a human serum albumin-based ArM that can robustly protect the catalytic activity of a bound ruthenium metal, even in the presence of 20 mM glutathione under in vitro conditions. To exploit this biocompatibility, the concept of glycosylated artificial metalloenzymes (GArM) was developed, which is based on functionalizing ArMs with N-glycan targeting moieties. As a potential drug therapy, this study shows that ruthenium-bound GArM complexes could preferentially accumulate to varying cancer cell lines via glycan-based targeting for prodrug activation of the anticancer agent umbelliprenin using ring-closing metathesis.

Tanaka, K.

BCSJ 2021, 94, 382-396, 10.1246/bcsj.20200316

In recent years, artificial metalloenzymes (ArMs) have become a major research interest in the field of biocatalysis. With the ability to facilitate new-to-nature reactions, researchers have generally prepared them either through intensive protein engineering studies or through the introduction of abiotic transition metals. The aim of this review will be to summarize the major types of ArMs that have been recently developed, as well as to highlight their general reaction scope. A point of emphasis will also be made to discuss the promising ways that the molecular selectivity of ArMs can be applied to in areas of pharmaceutical synthesis, diagnostics, and drug therapy.

Tanaka, K.

Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 2020, 96, 79-94, 10.2183/pjab.96.007

In order to harness the functionality of metals, nature has evolved over billions of years to utilize metalloproteins as key components in numerous cellular processes. Despite this, transition metals such as ruthenium, palladium, iridium, and gold are largely absent from naturally occurring metalloproteins, likely due to their scarcity as precious metals. To mimic the evolutionary process of nature, the field of artificial metalloenzymes (ArMs) was born as a way to benefit from the unique chemoselectivity and orthogonality of transition metals in a biological setting. In its current state, numerous examples have successfully incorporated transition metals into a variety of protein scaffolds. Using these ArMs, many examples of new-to-nature reactions have been carried out, some of which have shown substantial biocompatibility. Given the rapid rate at which this field is growing, this review aims to highlight some important studies that have begun to take the next step within this field; namely the development of ArM-centered drug therapies or biotechnological tools.