Shikimic acid is a naturally occurring cyclic organic compound found in plants and microorganisms. It serves as a foundational building block for other important substances, making it a subject of interest in scientific research and industrial applications.
What Shikimic Acid Is and Its Natural Sources
Shikimic acid is a seven-carbon compound with a distinct cyclic structure. Its chemical formula is C7H10O5, characterized by three hydroxyl groups and a carboxylic acid group. This arrangement allows it to participate in various biochemical reactions within organisms. It is a white crystalline solid that dissolves in water and has a melting point ranging from 186 to 190°C.
This organic acid is a common metabolite found in many plant species. Prominent natural sources include the Chinese star anise (Illicium verum), from which it was first isolated in 1885, the sweetgum tree (Liquidambar styraciflua), and various pine tree species. While present in most autotrophic organisms, it generally exists in low concentrations, making its extraction for commercial purposes a specific endeavor.
The Shikimate Pathway: Essential for Life
The shikimate pathway is a series of enzymatic reactions essential to life in plants, bacteria, fungi, algae, and some parasites. This metabolic route converts simple carbohydrate precursors into aromatic compounds. Specifically, it leads to the biosynthesis of aromatic amino acids such as phenylalanine, tyrosine, and tryptophan. These amino acids are building blocks for proteins and also serve as precursors for many other important molecules.
The pathway is absent in animals, so humans cannot produce these aromatic amino acids. Consequently, phenylalanine and tryptophan are considered “essential” amino acids in the human diet. Tyrosine is an exception, as it can be synthesized from dietary phenylalanine in humans. Beyond amino acids, the shikimate pathway also produces other important secondary metabolites, including lignins, alkaloids, and flavonoids, which contribute to plant structure, defense, and various biological functions. This metabolic difference makes the shikimate pathway a target for herbicides and antimicrobial agents that can selectively inhibit these organisms without affecting mammals.
From Plant Compound to Pharmaceutical Powerhouse
Shikimic acid is known for its role as a precursor in the industrial synthesis of oseltamivir, an antiviral drug marketed as Tamiflu. This medication treats and prevents influenza A and B infections, including strains like H1N1 and H5N1. The drug works by inhibiting the neuraminidase enzyme on the influenza virus surface, preventing its spread from infected cells.
Historically, the primary commercial source of shikimic acid for Tamiflu production was the Chinese star anise (Illicium verum). However, reliance on this natural source presented challenges, including fluctuating supply due to weather and the time it takes for star anise trees to mature. High global demand for Tamiflu, especially during flu pandemics, strained the star anise supply, leading to concerns about over-harvesting and sustainability.
To address these supply issues, alternative production methods have been implemented. Microbial fermentation, often using genetically engineered E. coli, has become a more efficient and cost-effective way to produce commercial quantities of shikimic acid. This shift reduced the pharmaceutical industry’s dependence on botanical sources. Beyond Tamiflu, shikimic acid and its derivatives are being investigated for other potential applications, including in cosmetics as deodorizing, anti-acne, and exfoliating agents, and for their antioxidant and antimicrobial properties.