451 4.4.0 Primary target IP address responded with:” 421 4.7.0 too many errors on this connection, closing transmision channel.” Attempted failover to alternate host, but that did not succeed. Either there are no alternate hosts, or delivery failover
Solution: The error 4.7.0 with 451 4.3.1 “Insufficient System Resources” signifies that the inbound mail submission has stopped due to resource constraint such as disk space being low on the volume where the queue database is located.
The following changes are required on EdgeTransport.exe.config file to disable the “BackPressure”. This is not recommended practice by Microsoft but when you are low on disk space this option can give you a breather.
Ste 1: Go to Exchange Serverbin directory and open EdgeTransport.exe.config file using Notepad.
Ste 2: Add the following key+value pair:
Step 3: Save the file and then restart the Microsoft Exchange Transport Service
The long term solution would be to either create extra storage on the volume hosting the queue database ormove to another volume that has plenty of free space. Here is the link to MS article on how you can move the queue.