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Acknowledgements We thank Junichi Ito for assistance in pathway analysis, Kaeko Tanaka, Syugo Hasuike, and Tomoya Shiina for technical assistance with the experiments, and Shoji clinic (Ibaraki, Japan) for providing umbilical cords

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In the next, extremely unfavorable elimination step (step 2), the conjugate base of the amine is kicked out from the tetrahedral intermediate: The reaction is driven to completion in a quick, irreversible deprotonation of the carboxylic acid by the newly formed RNH