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Although photoxenases gain interest for the photocontrol of enzymatic activity across various fields their design has so far remained challenging. To ease particularly the selection of AzoF incorporation sites, we have systematically evaluated a total of 85 positions that differ in their biochemical and biophysical features in the bi\u2010enzyme model system tryptophan synthase. Medium\u2010throughput production of AzoF\u2010containing variants, activity\u2010based screening and evaluation of photocontrol, and subsequent validation of the screening results allowed us to identify three site\u2010specific features that promote photocontrol with a success rate of up to 83% when combined. These features include positions in domains with catalytically important conformational transitions, positions determined via molecular dynamics based shortest path map analysis, and positions that originally contain a hydrophilic side chain. 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