I have seen this error many times (for various mako.py files) and it is often either when the user running it has insufficient privileges or the file permissions on a folder (could be several directories upstream) or a file have changed in some way. If you do a 'ps -ef | grep python' do you see the paster.py process running with your expected user? Do you use sudo to elevate the privileges when you run it? I use a 'galaxy' user but I execute run.sh (which I have created a service script for in /etc/init.d) with sudo while logged in as galaxy. Also you might want to do an 'ls -l' in the compiled_templates/ directory and look at the file permissions and file ownership. -Josh