See my personal notes. I do selfhost mail server, but on a vps to have a good IP

Being doing so for 20+ years and recently rebuilt the entire stack.

See https://wiki.gardiol.org/doku.php?id=email%3Astart

In short, I use postfix+dovecot, with opendmark and opendkim. Setup proper DNS email specific records and a few more steps.

Overall it runs fast and perfect on 4gb ram very old dual core atom CPU.

I have heard people have successfully utilised Mailcow without any issues for many years.

Personally gave it a try once but setting up ports, firewalls, virus scans, anti spams, dns felt too much effort for what I was going to use it for

Postfix and write a milter (mail filter), you can get them to interact a various points in the mail delivery.

I think most things can be accomplished within postfix

Use Stalwart as mailserver. Besides coming with sane defaults, it allows to put hooks into almost every mail stage. Those hooks can be sieve scripts, local binaries or http calls.

Ran the stack manually for decades, but spam makes it harder.

Run mailinabox now, it takes care of everything pretty well.

Modoboa is made with Django iirc, so that might be a good starting point

All your requirements are a given, except for wanting to do things in Python.

I definitely don't suggest self hosting email unless you don't care about losing messages occasionally