In 2022,Kim, Woojoo E.; Ishikawa, Fumihiro; Re, Rebecca N.; Suzuki, Takehiro; Dohmae, Naoshi; Kakeya, Hideaki; Tanabe, Genzoh; Burkart, Michael D. published an article in RSC Chemical Biology. The title of the article was 《Developing crosslinkers specific for epimerization domain in NRPS initiation modules to evaluate mechanism》.Category: alcohols-buliding-blocks The author mentioned the following in the article:
Nonribosomal peptide synthetases (NRPSs) are complex multi-modular enzymes containing catalytic domains responsible for the loading and incorporation of amino acids into natural products. These unique mol. factories can produce peptides with nonproteinogenic D-amino acids in which the epimerization (E) domain catalyzes the conversion of L-amino acids to D-amino acids, but its mechanism remains not fully understood. Here, we describe the development of pantetheine crosslinking probes that mimic the natural substrate L-Phe of the initiation module of tyrocidine synthetase, TycA, to elucidate and study the catalytic residues of the E domain. Mechanism-based crosslinking assays and MALDI-TOF MS were used to identify both H743 and E882 as the crosslinking site residues, demonstrating their roles as catalytic bases. Mutagenesis studies further validated these results and allowed the comparison of reactivity between the catalytic residues, concluding that glutamate acts as the dominant nucleophile in the crosslinking reaction, resembling the deprotonation of the Cα-H of amino acids in the epimerization reaction. The crosslinking probes employed in these studies provide new tools for studying the mol. details of E domains, as well as the potential to study C domains. In particular, they would elucidate key information for how these domains function and interact with their substrates in nature, further enhancing the knowledge needed to assist combinatorial biosynthetic efforts of NRPS systems to produce novel compounds In the experiment, the researchers used 4-Aminobutan-1-ol(cas: 13325-10-5Category: alcohols-buliding-blocks)
4-Aminobutan-1-ol(cas: 13325-10-5) is used in the synthesis of NSAIDs with anti-inflammatory properties. Also used in the synthesis of polyamine transport ligands with specificity against human cancers allowing easy access to specific cancer cells.Category: alcohols-buliding-blocks
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts