Positive feedback configurations with tTA in the last cistron consist of both essential and interdependent elements for regulated expression, with P hCMV * −1 and tTA at the perimeters of the multicistronic expression unit. This set-up harbours an intrinsic, auto-selective program which guarantees full length transcripts and maintains the functional integrity of all genetic elements encoded on this autoregulatory operon. Recently, a similar autoregulated dicistronic expression system was reported (Shocket et al., 1995; Hofmann et al., 1996; Zhang et al., 1997) , but only pTRIDENT-based or pQuattro-tTA systems allow one-step, autoregulated and auto-selective multigene metabolic engineering in industrially-relevant cell lines (Fussenegger et al., 1997b) .