The sunset paints the sky in hues of orange and purple, and as darkness descends, an ancient molecule awakens within countless organisms across the planet—from the tallest trees to the smallest bacteria, and within our own bodies. This is melatonin, a chemical timekeeper that has guided life through billions of years of evolution.
Imagine a biological substance so crucial that nearly every organism on Earth—from the simplest bacteria to complex humans—produces and utilizes it. This is melatonin, a molecule that first evolved in primitive bacteria approximately 2.5–3.5 billion years ago and has been retained throughout the evolution of life 2 6 . While commonly known as the "sleep hormone," melatonin's roles extend far beyond regulating our sleep-wake cycles. In plants, this indolamine compound, referred to as phytomelatonin, orchestrates growth, defends against stressors, and serves as a powerful antioxidant 1 8 .
The discovery of melatonin in plants and microorganisms has revolutionized our understanding of this ancient molecule, revealing a fascinating evolutionary tale written in the chemical language of tryptophan metabolism. This article explores the incredible journey of melatonin from its origins in primordial bacteria to its diverse functions in plants and animals today.
Melatonin's story begins in the dawn of life on Earth. During the Great Oxygenation Event around 2.5 billion years ago, photosynthetic bacteria began releasing oxygen into the atmosphere 2 . While oxygen enabled more efficient energy production, it also came with a cost: the generation of reactive oxygen species (ROS), toxic byproducts that damage cells 2 .
To combat this oxidative stress, primitive bacteria evolved melatonin primarily as an antioxidant and free radical scavenger 2 . The unique chemical structure of melatonin—an indole ring functionalized with a 3-amide group and a 5-alkoxygroup—made it exceptionally effective at neutralizing these toxic compounds 6 .
Primitive bacteria emerge, developing early metabolic pathways
Great Oxygenation Event triggers evolution of melatonin as antioxidant
Endosymbiotic events transfer melatonin production to eukaryotes
Melatonin functions diversely across all domains of life
According to the endosymbiotic theory, early eukaryotes engulfed these melatonin-producing bacteria, which eventually evolved into two key organelles: mitochondria (from α-proteobacteria) and chloroplasts (from cyanobacteria) 2 . These organelles retained their ability to produce melatonin, ensuring that all subsequent species could synthesize this critical molecule 2 .
| Type of Microorganism | Scientific Name | Melatonin Level | Key Enzymes |
|---|---|---|---|
| Yeast | Saccharomyces cerevisiae | 9.3–94.7 ng/mg protein | Not specified |
| Yeast | S. cerevisiae SCE-iL3-HM-40, 41, 42, and 43 | 0.04–1.93 mg/L | TPH, PTS, SPR, PCBD1, DHPR, DDC, AANAT, ASMT |
| Yeast | Saccharomyces cerevisiae QA23 | 0.0079–85.8813 ng/mL | TDC, T5H, DDC, SNAT, COMT, ASMT |
| Algae | Gonyaulax polyedra | 0.16–1.00 Cynst/t | Not specified |
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine with a molecular weight of 232.28 g/mol 6 . Its amphiphilic nature—both water- and fat-soluble—allows it to cross biological membranes easily and enter any cellular compartment 6 . This property enables melatonin to provide comprehensive protection against oxidative stress throughout the cell 6 .
While all organisms produce melatonin from the amino acid tryptophan, plants and animals have evolved different biosynthetic routes:
In animals, melatonin synthesis occurs primarily in mitochondria through a four-step process 3 8 :
Plants employ two potential pathways for melatonin synthesis 3 8 :
Tryptophan → Tryptamine → Serotonin → N-acetylserotonin → Melatonin
Tryptophan → 5-hydroxytryptophan → Serotonin → 5-methoxytryptamine → Melatonin
The key difference lies in the order of the decarboxylation and hydroxylation steps, with plants typically decarboxylating first while animals hydroxylate first 3 . Plants also utilize different enzymes, with caffeic acid-3-O-methyltransferase (COMT) sometimes serving the methylation function 8 .
| Aspect | Plants | Animals |
|---|---|---|
| Initial Step | Decarboxylation then hydroxylation | Hydroxylation then decarboxylation |
| Key Enzymes | TDC, T5H, SNAT, ASMT/COMT | TPH, AADC, AANAT, ASMT |
| Synthesis Sites | Mitochondria and chloroplasts | Primarily mitochondria |
| Pathways | Major and alternative pathways | Single pathway |
| Tryptophan Source | Synthesized internally | Must be obtained from diet |
To understand how researchers study melatonin's distribution within cells, let's examine a groundbreaking experiment that localized melatonin in human salivary glands using transmission electron microscopy .
The experiment revealed that melatonin was predominantly located in secretory granules of glandular cells, but also clearly present in mitochondria . In striated duct cells, mitochondrial melatonin staining was even more prominent than in glandular cells .
These findings provided the first ultrastructural evidence of melatonin within human salivary gland mitochondria, supporting the theory that mitochondria are not just energy producers but also important sites for melatonin synthesis and action . The presence of melatonin in mitochondria aligns with its proposed original function as an ancient antioxidant protecting these vital organelles from oxidative damage 2 .
| Cellular Structure | Parotid Gland | Submandibular Gland |
|---|---|---|
| Secretory Granules | 88.1% (high intensity) | 49.5% (medium intensity) |
| Mitochondria | 34.1% (low intensity) | 29.7% (low intensity) |
| Endoplasmic Reticulum | Present | Present |
| Nuclei | Few gold particles | Few gold particles |
Studying melatonin requires specialized tools and reagents. Here are essential components of the melatonin researcher's toolkit:
Used in immunogold staining and other localization techniques to identify and track melatonin within tissues and cells .
Experimental compounds that block the first step of melatonin synthesis in animals, helping researchers understand melatonin's functions.
Tools for measuring the activity of key enzymes in the melatonin synthesis pathway, allowing researchers to quantify melatonin production capacity.
High-performance liquid chromatography coupled with mass spectrometry enables precise measurement of melatonin levels in tissues, cells, or biological fluids.
Used to study plant melatonin biosynthesis by interfering with the initial step in the phytomelatonin pathway.
Melatonin's journey from bacterial antioxidant to multifunctional signaling molecule in plants and animals represents one of evolution's most fascinating stories. In plants, phytomelatonin continues to serve as a growth regulator, stress defender, and ecological signal 1 8 . In animals, it has expanded its roles to include circadian rhythm regulation, immune modulation, and seasonal reproduction control 2 5 .
As we continue to unravel the secrets of this ancient molecule, we gain not only deeper insights into fundamental biological processes but also potential solutions to challenges in medicine, agriculture, and environmental sustainability.
The next time you enjoy a restful night's sleep or admire a thriving plant, remember the ancient molecular guardian that has been working behind the scenes for billions of years—quietly regulating, protecting, and connecting all life on Earth through the darkness and light.