Approaching transglutaminase from Streptomyces bacteria over three decades

Area of Science:

• Biochemistry
• Enzymology
• Biotechnology

Background:

• Transglutaminases (TG) are enzymes catalyzing protein cross-linking and modification.
• Microbial transglutaminases (MTG) from Streptomyces are increasingly used for therapeutic protein modification.
• Streptomyces mobaraensis MTG (SmMTG) is a prominent representative enzyme.

Purpose of the Study:

• To review the occurrence, production, structure, catalysis, and substrates of MTG enzymes.
• To discuss biotechnological applications of SmMTG.
• To provide new insights into the catalytic mechanisms of SmMTG and related transglutaminases.

Main Methods:

• Literature review of studies on MTG occurrence, production, structure, and catalysis.
• Analysis of SmMTG and other transglutaminase catalytic mechanisms.
• Discussion of substrate protein structure and function from S. mobaraensis.

Main Results:

• SmMTG selects glutamine donor proteins via subsites in its front vestibule and utilizes distinct lysine pockets.
• Substrate flexibility is crucial for SmMTG accessibility, more so than the glutamine environment.
• The absence of lysine donor subsites suggests protein self-assembly before enzymatic cross-linking.

Conclusions:

• Further study of natural substrate proteins and their interactions is recommended to fully understand SmMTG catalysis.
• Understanding these mechanisms can optimize the use of MTG in protein modification and therapeutic applications.