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

## TL;DR

This study shows how cinnamic acid inhibits pigment production in bacteria by targeting a key enzyme, offering insights into compound regulation.

## Contribution

The paper reveals cinnamic acid's competitive inhibition of AntI, providing atomic-level insights into pigment biosynthesis regulation.

## Key findings

- Cinnamic acid inhibits AQ-256 biosynthesis by targeting the enzyme AntI.
- CA induces structural changes in AntI, leading to reversible inhibition.
- There is an inverse correlation between cinnamic acid and anthraquinone pigment production.

## Abstract

Photorhabdus strains, Gram-negative
bacteria pathogenic
to insect larvae, produce two signature compounds: the multifunctional
isopropylstilbene (IPS), known for its antibiotic, insecticidal, and
immunosuppressive activities, and orange-to-red pigmented anthraquinones
(AQs), which attenuate oxidative stress. Here, we demonstrate an inverse
correlation between the production of AQs and cinnamic acid (CA),
the primary precursor for IPS formation in the model strain P. laumondii TTO1. Metabolic and proteomic analyses following
CA treatment show that CA inhibits AntI, a key enzyme in the final
step of AQ-256 biosynthesis. The crystal structure of AntI in complex
with CA reveals that cinnamic acid functions as a competitive inhibitor
by inducing specific structural rearrangements in the lyase, resulting
in noncovalent, reversible inhibition. These findings provide atomic
insights into the intricate regulatory control of pigment biosynthesis
and the production of bioactive compounds.