The Isopropylstilbene Precursor Cinnamic Acid Inhibits Anthraquinone Pigment Production by Targeting AntI

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Photorhabdus bacteria produce bioactive compounds, including isopropylstilbene (IPS) and anthraquinones (AQs).
• Anthraquinones (AQs) are pigments that attenuate oxidative stress.
• Isopropylstilbene (IPS) exhibits antibiotic, insecticidal, and immunosuppressive activities.

Purpose of the Study:

• To investigate the inverse correlation between anthraquinone (AQ) production and cinnamic acid (CA) in Photorhabdus laumondii TTO1.
• To elucidate the mechanism by which cinnamic acid (CA) affects anthraquinone (AQ) biosynthesis.
• To determine the structural basis of cinnamic acid's (CA) inhibitory effect on AQ biosynthesis.

Main Methods:

• Metabolic and proteomic analyses were performed following cinnamic acid (CA) treatment.
• The crystal structure of the enzyme AntI in complex with cinnamic acid (CA) was determined.
• Enzyme inhibition assays were conducted to confirm the mechanism of action.

Main Results:

• An inverse correlation was observed between anthraquinone (AQ) production and cinnamic acid (CA) levels.
• Cinnamic acid (CA) was found to inhibit AntI, a key enzyme in AQ-256 biosynthesis.
• Structural analysis revealed that cinnamic acid (CA) acts as a competitive, noncovalent, and reversible inhibitor of AntI.

Conclusions:

• Cinnamic acid (CA) regulates pigment biosynthesis in Photorhabdus bacteria by inhibiting AQ production.
• The findings provide atomic-level insights into the regulation of bioactive compound synthesis.
• This study clarifies the intricate interplay between precursor availability and secondary metabolite production in bacteria.