I wonder for curiosity and concerns; how and why the new DNA letters have not already evolved and do not already feature in the present range of living species?

I wonder for curiosity and concerns; how and why the new DNA letters have not already evolved and do not already feature in the present range of living species? Should a firm understanding of this, no matter how far off, not be a prerequisite to aspirations of mass production of novel proteins and new lifeforms featuring them? Novel DNA and proteins - after billions of years natural CI... we better be sure to have a damn good incident response capability! But do we?