Overall, all three reference levels of theory give relatively similar benchmarking outcomes. For metalloenzymes, which are more sensitive to the choice of reference value, we recommend CPS(6,7) as a low cost way of improving the accuracy of DLPNO-CCSD(T) in terms of reducing the PNO truncation error-if TightPNO calculations are feasible for a system, then so is CPS(6,7) as the additional T CutP N O = 10 -6 calculations are significantly more computationally efficient. The relative rankings of the DFAs are not significantly impacted, however, when CPS (5,6) is used instead of TightPNO. The CPS (5,6) BHs and REs are not necessarily converged with respect to T CutP N O so they may not be adequate for high level analysis of specific enzyme energetics, but this level of theory is a reasonable option for an assessment of density functionals when lower cost methods are required. This is particularly useful in extending the applicability of DLPNO-CCSD(T) to benchmark sets containing larger systems. For organic enzymes, any changes in the performance of the DFAs with the three reference levels of theory seem to be negligible. We therefore conduct further analysis using the entire EN-ZYMES22 set, to see whether this holds across a larger set. As well as the models of 4-OT, AspDC, HheC and HKMT included in the small test set, ENZYMES22 contains additional models of AspDC (one smaller and one larger model), HheC (one larger model) and HKMT (two smaller models); all of these follow the same mechanisms shown in figure . This extends the range of system sizes represented in our tests in both directions, with ENZYMES22 con- taining models from 27 to 112 atoms.