Peptidases are indispensable tools in biotechnology and chemical biology. However, the enzyme repertoire for the selective hydrolysis of dl-amide bonds in peptides is small. Here, we describe novel dl-peptidases that mediate complex microbial interactions. These enzymes, Lip3 and Lip7, convert lipopeptides into potent amoebicidal agents via selective dl-peptide bond cleavage. Using structural analyses and mutagenesis, we identified an unusual Ser–Lys–Lys–Tyr catalytic tetrad required for dl-specificity. Despite their high structural similarity, both enzymes show distinct substrate preferences: Lip3 acts primarily as a carboxypeptidase, removing a single C-terminal residue, while Lip7 excises a tripeptide. Although their substrate scopes are broad, they are highly specific with regard to their respective cutting sites. These features make these dl-peptidases powerful tools for elucidating the structure of complex peptide-based natural products, including tensin and WLIP. Overall, this work elucidates the molecular mechanisms of cooperative microbial defense and provides a new enzymatic toolbox for biocatalysis and natural product discovery.

The past decades have seen significant expansion of the nucleic acid space with the development of modified artificial base pairs based on natural nucleic acid analogues and even entirely new designed base pairs. This expansion has led to tremendous potential for applications such as site-specific labeling and structural investigations. However, natural nucleic acids rely strongly on hydrogen bonding as the attraction force, which has driven the development of artificial base pairs that adapt this mechanism. To achieve orthogonality with natural bases, unnatural base pairs with alternative attraction forces, such as hydrophobic interactions, have been developed which however can perturb duplex structures. Our work introduces a completely newly designed artificial base pair that leverages halogen bonding (R–Hal···) as a directional hydrogen bonding-like interaction. We report computational studies that led to the development of this novel unnatural base pair and its synthesis. Our results demonstrate the successful acceptance of a bulky iodinated nucleoside triphosphate by KlenTaq DNA polymerase, enabling the selective enzymatic synthesis of a DNA strand containing the dIIPO–doIPP base pair. Our work presents the first demonstration of a novel base pair with halogen bonding potential that is enzymatically incorporated into DNA.

Doping cholesteric liquid crystals (CLCs) with photoresponsive chiral molecules is an effective strategy for devising responsive soft materials, as it allows for the phototuning of the noncovalent interactions in the CLCs, and hence, their helical pitch and optical properties. Here we describe the use of tribenzotriquinacene-based (TBTQ) hydrazone and azobenzene chiral dopants in the modulation of the helical pitch of the LC host, 5CB. The unique C3-symmetry of the TBTQ scaffold enhances the noncovalent interactions with the host and thus the chiral information transfer, resulting in helical twisting power (β) values as high as 147 μm–1. Notably, the TBTQ hydrazone exhibits an unusual deviation from trends observed so far in previous studies, resulting in larger β values for the Z isomer rather than the E one. Moreover, the overall β values for the hydrazone-based dopants are unexpectedly higher than those of the azobenzene dopants. These results indicate that the host/guest interactions are better when the photoswitchable chiral dopant is more rigid, as is the case with the H-bonded Z state of the hydrazone. The large β values and excellent miscibility of the hydrazone-based dopants in 5CB allowed us to design films that reflect visible structural color. The properties of the azobenzene-based dopants precluded their use in such applications. By codoping 5CB with hydrazone and azobenzene derivatives of opposite chirality, we demonstrated reversible handedness inversion upon photoswitching, providing a versatile soft material platform for reconfigurable photonic materials and colorimetric display technologies.

Oxidatively induced reductive elimination (OIRE) is a powerful strategy for the formation of carbon–carbon bonds and has been widely employed in late transition metal catalysis. In contrast, early tra...