Expression and Subcellular Localization of Lanthipeptides in Human Cells.

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Cyclic peptides, including ribosomally synthesized and post-translationally modified peptides (RiPPs), are of significant interest in therapeutics and biotechnology.
• Their constrained conformations offer advantages over linear peptides, including enhanced stability against proteolytic degradation.

Purpose of the Study:

• To develop a novel expression system for producing structurally diverse lanthipeptides and their derivatives within mammalian cells.
• To demonstrate the feasibility of targeting these lanthipeptides to specific cellular organelles, including the nucleus, endoplasmic reticulum, and plasma membrane.

Main Methods:

• Development of a mammalian cell-based expression system for lanthipeptide production.
• In vivo expression and subcellular localization studies of synthesized lanthipeptides.
• Demonstration of targeting lanthipeptides to the nucleus, endoplasmic reticulum, and plasma membrane.

Main Results:

• Successful production of structurally diverse lanthipeptides and derivatives in mammalian cells.
• Demonstrated successful targeting of lanthipeptides to the nucleus, endoplasmic reticulum, and plasma membrane.
• Established a platform for in vivo screening of lanthipeptide-based inhibitors.

Conclusions:

• The developed expression system facilitates the production and intracellular targeting of lanthipeptides in mammalian cells.
• This system enables the screening of lanthipeptide-based cyclic peptide inhibitors for native, organelle-specific protein-protein interactions.
• This work opens new possibilities for therapeutic and biotechnological applications of cyclic peptides.