Is Benzoic Acid Safe? Exploring Its Impact on Protein Structure and Function

Benzoic acid (BA) is a widely used additive in the food, pharmaceutical, and cosmetic industries. It serves as a flavoring agent and has antimicrobial properties. However, the safety of BA has been a subject of controversy, and its use as a Generally Recognized as Safe (GRAS) substance remains uncertain. This study aims to investigate the interaction between BA and an intrinsically disordered protein (IDP) under pH conditions relevant to its commercial use. The structural changes induced by BA were examined using NMR, fluorescence, and high-resolution microscopy.

The Controversy Surrounding BA:

BA is extensively utilized due to its antimicrobial and flavor-enhancing properties. It is regulated by international bodies such as the Codex Alimentarius Commission (CAC) to ensure consumer safety. BA is also found naturally in microbes, fruits, and eukaryotic cells, suggesting potential health benefits. However, concerns about its adverse effects have been raised. Studies have associated BA with attention deficit hyperactive disorder (ADHD) symptoms, urticaria, allergic reactions, and possible neurotoxic effects and fetal abnormalities.

Investigating Protein Interactions:

To shed light on the impact of food additives on proteins, this study focused on the interaction between BA and an IDP. IDPs play crucial roles in protein networking and often lack a defined 3D structure. The research utilized Arabidopsis thaliana phloem protein 16-class 1 (AtPP16–1 Q9M2T2), an IDP involved in mRNA transport, as a model system. The NMR structure of AtPP16–1 revealed a predominantly disordered structure with short β-strands and an α-helix.

Effects on Protein Structure:

The study found that even at concentrations significantly lower than recommended by regulatory bodies, BA induced the formation of amyloid fibrils in AtPP16–1. This suggests a potent aggregating effect of BA on IDPs. The transformation of the protein into a denatured aggregated mesophase, followed by the reconfiguration into amyloid fibrils, highlights the structural impact of BA.

Implications and Future Research:

Understanding the influence of food additives on protein structure and function is crucial for ensuring the quality and efficacy of pharmaceutical and food products. The findings of this study emphasize the need for comprehensive investigations into the effects of preservatives on metabolites, proteins, nucleic acids, and lipids. The role of IDPs in these interactions should not be overlooked. Further research in this area could provide valuable insights into the development of safer alternatives to BA and other food additives.

The safety of benzoic acid as a food additive remains a subject of debate. This study demonstrates the propensity of BA to induce structural transformations in an intrinsically disordered protein, leading to the formation of amyloid fibrils. These findings underscore the importance of thorough evaluation of the effects of food additives on protein structure and function. By investigating such interactions, researchers can gain a better understanding of the implications for food quality and human health.