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I don't see why not. SMTP can work over both TCP and UDP (both of which supported by NAT Gateway). That being said, I believe EC2 instances throttle port 25 by default (see: https://docs.aws.amazon.com/AWSEC2/latest/UserGuide/ec2-resource-limits.html and https://aws.amazon.com/premiumsupport/knowledge-center/ec2-port-25-throttle/)
answered 6 years ago
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