Architecture of an asymmetric mycobacterial short chain/long chain acyl-CoA carboxylase

Endogenous extraction has revealed a mycobacterial hybrid acyl-CoA carboxylase (ACCase) complex exhibiting distinct long-chain (LC) and short-chain (LC) acyl-CoA carboxyl transferase (CT) activities. The presence of two different CT subunits (AccD4, AccD5) is triggered by a unique AccE5 dimer. AccE5 also generates a flexible biotin carboxylase (BC) / CT arrangement through a 9-stranded {beta}-barrel, which rotates the entire BC assembly by [~]90{degrees} in the presence of acyl-CoA substrates. These data demonstrate that asymmetric, multi-substrate ACCases differ fundamentally from symmetric, single-substrate ACCases.