While many bioprocesses to generate enzymes approximate biotransformations in which commercial (usually vegetable) protein sources support enzyme production, the utilization and processing of amino acids masks metabolic imbalances.
With an endoprotease produced by a simple bacterium, the process exhibited classical nitrogen starvation. In reality the medium was awash with “nitrogen” in the form of peptides that could no longer be accessed because ancillary proteases were themselves destroyed so rapidly that the fermentation became self-limiting. Radically different strategies of managing growth and productivity in a fed-batch mode were successful developments.