1. Limited Post-translational Modifications: Bacteria lack the complex machinery found in eukaryotic cells for post-translational modifications (PTMs). These modifications, such as phosphorylation, glycosylation, and acetylation, are crucial for the proper folding, stability, and function of many proteins. This limitation can hinder the production of proteins that require these modifications for activity.

2. Potential for Toxicity: Some proteins, especially those with cytotoxic or immunogenic properties, can be detrimental to the bacterial host cells when expressed at high levels. This can lead to reduced protein production or even cell death, making it challenging to obtain large quantities of the desired protein.

These limitations are not insurmountable, but they need to be considered when designing and implementing bacterial gene expression systems.