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Publication Abstract from PubMed

Non-ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N- and C-terminal docking domains ((N/C) DDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of "designer" NRPS from proteins that normally do not interact. The multiprotein "peptide-antimicrobial-Xenorhabdus" (PAX) peptide-producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small (C) DD of PaxA cooperates with its preceding thiolation (T1 ) domain to bind the (N) DD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems.

Cooperation between a T Domain and a Minimal C-Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS.,Watzel J, Duchardt-Ferner E, Sarawi S, Bode HB, Wohnert J Angew Chem Int Ed Engl. 2021 Jun 14;60(25):14171-14178. doi:, 10.1002/anie.202103498. Epub 2021 May 14. PMID:33876501^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.