Total Chemical Synthesis of Aureocin A53, Lacticin Q and Their Enantiomeric Counterparts
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Aureocin A53 (AucA) and lacticin Q (LnqQ) are class IId bacteriocins that display broad-spectrum activity against Gram-positive bacteria in the nanomolar range, of which their modes of action is unclear and their synthesis has not been reported. Here, we reported the chemical synthetic routes of AucA and LnqQ, enabled through the technique of native chemical ligation. To demonstrate the versatility of the syntheses, we prepared their enantiomeric counterparts, D-AucA and D-LnqQ, comprised of entirely D-amino acids. X-ray crystal structure of AucA obtained through racemic protein crystallography at 1.13 Å indicates unique Lys-Trp-sulfate network. This work lays foundations for gaining further mechanistic insights into these potent bacteriocins through total chemical synthesis.