Shikimic acid, often referred to by its anionic form, shikimate, is an organic compound found ubiquitously in plants and microorganisms. This seven-carbon molecule is a cycloalkene, characterized by a six-membered ring structure containing one double bond and several hydroxyl groups. Although its name is derived from the Japanese Illicium plant, the molecule’s profound significance extends into biochemistry and pharmaceutical manufacturing. It serves as a central hub in natural metabolism, acting as a molecular bridge that connects simple sugars to a vast array of complex aromatic compounds. Understanding this molecule reveals its deep impact on both the natural world and modern medicine.
What Is Shikimic Acid and Where Is It Found
Shikimic acid is a hydroaromatic compound with the chemical formula C\(_{7}\)H\(_{10}\)O\(_{5}\), classified structurally as a cyclitol and a cyclohexanecarboxylic acid. Its precise chemical configuration, including three stereogenic carbons, makes it a valuable starting material for complex organic synthesis. The compound was first isolated in 1885 from the Japanese flower shikimi (Illicium anisatum), but it is present in nearly all autotrophic organisms, including plants, bacteria, and fungi.
While many plants produce the acid, it is typically found in low concentrations because it is a constantly recycled biosynthetic intermediate. The most famous natural source is the Chinese star anise (Illicium verum), an evergreen tree fruit used as a spice. The dried fruits of star anise contain a relatively high concentration, yielding shikimic acid between 3% and 7% by weight.
This concentration made star anise the primary commercial source for decades. Alternative sources, such as the seeds of the American sweetgum fruit (Liquidambar styraciflua), yield around 1.5% shikimic acid. However, because the molecule is a transient metabolite, high-volume industrial production has increasingly moved toward engineered biological systems rather than relying solely on plant extraction.
The Essential Biological Function
The existence of shikimic acid is defined by its role as an intermediate in a metabolic route known as the Shikimate Pathway. This seven-step biochemical process is the only known route used by plants, bacteria, fungi, algae, and certain parasites to synthesize various crucial metabolites. Its primary purpose is the production of the three aromatic amino acids: phenylalanine, tyrosine, and tryptophan.
This pathway is completely absent in humans and other animals, which is a fundamental distinction in metabolism. Since humans cannot produce these aromatic amino acids internally, they must acquire them through their diet, classifying them as essential amino acids. The Shikimate Pathway acts as a bridge between simple carbohydrate precursors, such as phosphoenolpyruvate and erythrose-4-phosphate, and complex aromatic ring structures.
The shikimate pathway is also a major gateway for producing specialized metabolites in plants. These compounds include lignin, which provides structural integrity to plant cell walls, and various flavonoids and tannins, which serve protective functions.
Shikimic Acid as a Key to Antiviral Medicine
The global profile of shikimic acid changed due to its indirect role in modern antiviral medicine. It is a starting material used in the industrial synthesis of Oseltamivir Phosphate, the active compound in the influenza drug Tamiflu. The molecule’s specific cyclohexene ring structure and arrangement of hydroxyl groups make it chemically suitable for conversion into the antiviral drug’s complex structure.
Oseltamivir is a neuraminidase inhibitor that blocks the neuraminidase enzyme on the surface of influenza viruses, preventing new viral particles from escaping an infected cell. The natural chirality, or handedness, of shikimic acid is advantageous because it provides the correct stereochemistry needed to build the active form of the drug efficiently.
Initial reliance on natural extraction from star anise proved problematic during periods of high demand, such as the avian flu scares in the mid-2000s. This dependence on a single, seasonal agricultural product caused supply shortages and price volatility. To secure a stable and scalable supply, researchers invested in alternative production methods. These methods include the metabolic engineering of microorganisms, such as E. coli, to produce large quantities of shikimic acid through fermentation, mitigating the risk of future supply chain disruptions.
Emerging Applications in Science and Industry
The versatility of shikimic acid’s chemical structure makes it a subject of extensive research beyond its role as a precursor for Tamiflu. In the agricultural sector, the Shikimate Pathway is the target of certain herbicides, such as glyphosate. These compounds inhibit an enzyme in the pathway, halting the growth of weeds without affecting animals, which lack the pathway.
In pharmaceutical development, the molecule is being explored as a platform for synthesizing other complex medicinal compounds. Derivatives of shikimic acid are being investigated for potential anticoagulant and antithrombotic activities useful in managing blood clotting disorders. It is also being studied as a precursor for certain anti-cancer agents and antibiotics.
The compound has also found a niche in the cosmetic and personal care industries due to its mild exfoliating and antimicrobial properties. Research suggests shikimic acid may be an effective ingredient in formulations for:
- Anti-acne products
- Anti-dandruff treatments
- Deodorizing products
- Managing chronic skin conditions, due to its antioxidant and anti-inflammatory properties