iRule to forward traffic based in sender domain

i would try to solve this on your anti-spam appliance, it is much more email / SMTP aware so hopefully can have rules like this.

do you already have this active on the BIG-IP for one domain? or does the BIG-IP just forward all traffic now? or isn't it involved at all?

the general approach would be to collect the SMTP communication till you receive the domain and then choose a pool for the different gateways. but SMTP communication isn't that straight forward like with HTTP which contains the "domain" (Host header) in every request.

so you will end up with something like suggested here: https://devcentral.f5.com/questions/irule-based-on-smtp-receiver-domain

which the question asker there already finds overly complex.