FabG: from a core to circumstantial catalyst.

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Fatty-acid synthesis II (FAS II) is a core prokaryotic pathway for synthesizing fatty acids, biotin, and lipoic acid.
• Key enzymes FabG and FabI interact with Acyl-carrier protein (ACP), a flexible binding partner for substrates of varying lengths.

Purpose of the Study:

• To explore the functional flexibility of FabG and FabI enzymes within the FAS II pathway.
• To highlight the industrial applications of FabG's catalytic versatility.
• To position FAS II as a potential antibacterial drug target.

Main Methods:

• Analysis of protein-protein interactions between FAS II dehydrogenases and Acyl-carrier protein.
• Investigating the catalytic capabilities of FabG for producing chiral synthons and secondary metabolites.
• Comparative genomics to understand the evolutionary context of FAS II in prokaryotes versus eukaryotes.

Main Results:

• Protein-protein interactions between FabG/FabI and ACP broaden enzyme active sites, conferring catalytic flexibility.
• FabG demonstrates broad utility in catalyzing the synthesis of diverse industrial compounds.
• FAS II represents a relic gene pool in eukaryotes and a viable antibacterial drug target.

Conclusions:

• The flexible nature of FabG and FabI, mediated by ACP interaction, is crucial for diverse biochemical synthesis.
• FabG's adaptability suggests its potential as a progenitor enzyme for complex dehydrogenases in biotechnology.
• Targeting the FAS II pathway offers a promising strategy for developing new antibacterial agents.