Crystallographic Deciphering of Spontaneous Self‐Assembly of Achiral Calciphores to Chiral Complexes

Abstract

Thiapyricins (TPC-A/B, 1 and 2), which are new metallophore scaffolds exhibiting selective divalent cation binding property, were produced in response to metaldeprived conditions by Saccharothrix sp. TRM_47004 isolated from the Lop Nor Salt Lake. TPCs represent a thiazolylpyridine skeleton of a calcium-binding natural product, calciphore, owing to the selectivity to calcium ions among diverse metal ions. The thiapyricins exhibited notable cocrystalline characteristics of the apo-and holo-forms with racemic enantiomers comprising a pair of space isomers in a Δ/Λ-form. Therefore, we postulated a mechanism for the four-hierarchical self-assembly of achiral natural products into chiral complexes. Furthermore, their metal-chelating trait aided the adaptation of the host during metal starvation by increasing the production of TPCs. This study presents a structural paradigm of a new calciphore, provides insight into the mechanism of natural product assembly, and highlights the causality between the production of the metallophore and metallic habitats.