BTG13-related metalloenzymes: Atypical non-heme iron-dependent dioxygenases with unusual coordination patterns and catalytic mechanisms

Abstract

Owing to their diverse coordination patterns and catalytic mechanisms, non-heme iron-dependent dioxygenases catalyze a variety of biochemical reactions involved in the synthesis of numerous natural products and valuable compounds. Recently, we discovered a novel and atypical non-heme iron-dependent dioxygenase, BTG13, that features a unique coordination center consisting of four histidines and a carboxylated lysine (Kcx). This enzyme catalyzes the C-C bond cleavage of anthraquinone through two unconventional steps, with modified Kcx playing a key role in facilitating these processes, as revealed by molecular dynamics simulations and quantum chemical calculations. Phylogenetic analyses and other studies suggest that BTG13-related metalloenzymes are widespread in various organisms. Here, we highlight the significance of this new class of non-heme iron-dependent oxygenases and their potential as novel tools for practical applications in synthetic biology.

Keywords

BTG13 / Carboxylated lysine / Catalytic mechanism / Coordination pattern / Non-heme iron dioxygenase

Declaration of AI in Scientific Writing

The authors declare that no AI was used in scientific writing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Zhiwei Deng: Writing - review & editing, Writing - original draft, Validation, Software, Methodology, Investigation, Formal analysis, Data curation. Zhenbo Yuan: Validation, Resources, Investigation. Zhengshan Luo: Validation, Resources, Formal analysis. Yijian Rao: Writing - review & editing, Supervision, Project administration, Funding acquisition, Conceptualization.

Acknowledgements

This work was funded by the National Natural Science Foundation of China (32270082 and 22207044), the Natural Science Foundation of Jiangsu Province (BK20202002), the Basic Research Program of Jiangsu and the Jiangsu Basic Research Center for Synthetic Biology (BK20233003).

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