We thank all reviewers for their insightful comments and suggestions, which will be incorporated into the revised

The concurrent work G2Gs presents a similar two-step framework, while our method is more general and scalable. We keep muted about G2Gs before its conference version is available since we have some concerns about it. This discussion will be included into our revised version. Atom mapping is optional for our method. The synthon approach can also work for reactions without provided atom mapping (L208-212).