Synthesis, Bioproduction and Bioactivity of Perillic Acid-A Review

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Perillic acid (PA) is a limonene derivative with underexplored biological properties compared to related monoterpenes.
• Existing literature often describes PA in mixtures, with limited focus on the pure compound.
• PA exhibits potential anticancer activity, primarily through interference with protein prenylation.

Purpose of the Study:

• To comprehensively review perillic acid (PA), covering its origin, synthesis, and biological activities.
• To evaluate current methods for obtaining PA, including organic synthesis and biotransformation.
• To highlight the pharmacological potential of PA, particularly in preclinical oncology.

Main Methods:

• Literature review of studies on perillic acid (PA) synthesis and bioactivity.
• Analysis of organic synthesis routes from limonene and other precursors.
• Evaluation of biotransformation processes using bacteria and yeasts.
• Review of in vitro pharmacological data, focusing on anticancer mechanisms.

Main Results:

• Organic synthesis of PA from limonene is multi-step and often low-yielding; (-)-β-pinene epoxide offers a more economical route to (-)-PA.
• Microbial biotransformation by bacteria and yeasts provides a greener alternative for producing PA with high purity.
• PA's primary anticancer mechanism involves inhibiting the prenylation of oncogenic proteins, crucial for cancer cell proliferation.

Conclusions:

• Microbial production of PA presents a promising, environmentally friendly approach for scalable manufacturing.
• PA's anticancer properties warrant further investigation, especially regarding its mechanism of action and therapeutic applications.
• Significant opportunities exist for advancing PA research in preclinical oncology and exploring its full pharmacological potential.