Post-translational formation of strained cyclophanes in bacteria

Post‐Translational Formation of Aminomalonate by a Promiscuous Peptide‐Modifying Radical SAM Enzyme

“…SjiB consists of an N-terminalS PASM family of rSAM domain and aC-terminal HExxH domain;the latter domain was suggestive of metalloprotease activity. [31,38] 1, SjiA 51-60 -2 exhibited as eries of ba nd y ions within the tobe-cyclized FxS motif (Figure 2E and Figure S3), indicating that the FxS motif was not cross-linked in 2.M ore importantly,t he À2Dam odification was observed exclusively on the Ser residue within the FxS motif (Figure 2E), which is reminiscent of formylglycine (FGly), astructural motif can be formed by anaerobic sulfatase maturation enzyme (anSME). [40][41][42] This proposal is consistent with the observation of the + 16 Da Angewandte Chemie modifications, [43] but is reminiscent of Ama, am alonatecontaining amino acid.…”

“…See Note S1 for detailed sequences. SjiB consists of an N-terminalS PASM family of rSAM domain and aC-terminal HExxH domain;the latter domain was suggestive of metalloprotease activity [31,38]. (B) HR-MS characterization of SijA modified by SjiB-399 in vivo (1).…”

A roadmap for metagenomic enzyme discovery

“…80 In particular, radical SAM enzymes post-translationally modify many RiPPs through epimerization of L-to D-amino acids, 19,81 excision of tyramine to form a-keto moieties, 82 and formation of intramolecular crosslinks including strained cyclophane macrocycles. 83 Radical SAMs also play a role in the biosynthesis of hypermodied tRNA bases 84 and nucleoside-based natural products through C-C bond extension at C5 0 of ribose rings to connect nucleosides to structurally diverse functional groups. 85 A number of other enzyme classes not covered in detail here also were predicted to have remarkable across-EC-class reaction diversity.…”

Organometallic AlaM reagents for umpolung peptide diversification

“…[97][98][99] Among those, methods that can selectively connect the aromatic ring in the form cyclophane-type frameworks can facilitate the discovery of novel bioactive compounds. 13,100,101 The rigid, planar, and hydrophobic aromatic rings support the cyclic structures, can be fully fitted into the main skeleton of the cyclic peptide molecule, and are amenable to structural modifications. The non-canonical aryl linkers can stabilize secondary structures and promote hydrogen bonding that can be beneficial for optimizing membrane permeability and bioavailability.…”