Proposed hypothetical folding model for the <i>B. glumae</i> lipase based on our observations.

<p>We suggest that the biogenesis of lipase encompasses several steps: (i) after translation, the lipase is translocated over the inner membrane in a Sec-dependent and therefore unfolded conformation step with the concomitant removal of the leader peptide; (ii) LipA folds through a short-lived transient molten globule-like state (LipA_g) that was observed under moderate guHCl concentrations into a more compact and near native folding intermediate (LipA_i); (iii) rather than LipA_g, this near-native intermediate LipA_i is the substrate that specifically interacts with Lif and (iv) becomes fully folded and activated into the native LipA_n fold through a contact-assisted folding mechanism. Several questions remain to be addressed regarding the disulfide bond formation, the incorporation of the calcium ion, how LipA_n is released from Lif, as well as the chronology of these events. This hypothetical model is only based on <i>in vitro</i> observations and as detailed thermodynamic and kinetic data remain elusive, the arrows only represent the subsequent transitions in the lipase folding landscape, while they do not enclose any absolute kinetic or equilibrium information.