For these kind of issues, as an initial step, you need check the below details:

*Please confirm that the DNS records are set for the domain. Also it has been propagated.

*confirm that the rDNS entry for your main IP address is set which may cause this issue.

*If all those are Yes, then I would suggest switching off the SMTP Tweak and trying again. You can also try after restarting Exim. [/etc/init.d/exim restart]

*Any time you get 550 sender failed error you need to check your passwd and shadow permissions in /home/username/etc/ they should be 644 and 640 respectively.

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