Discovery: The Sulfur Amino Acid
In 1922, American biochemist John Howard Mueller was working at the Rockefeller Institute, studying what nutritional factors bacteria needed to grow. He was systematically testing different protein hydrolysates — broken-down proteins — as growth media for Streptococcus hemolyticus. When he isolated a new sulfur-containing compound from casein (milk protein), he didn't immediately appreciate what he'd found.
The new substance was named methionine, derived from "methio" (a Greek root for sulfur-containing compounds) and "-ine" (the suffix for amino acids). It was one of the last amino acids to be discovered — amino acid chemistry had been going on for over a century by 1922, and the field thought most of the standard amino acids had already been found. Methionine was a late surprise.
"Every protein ever synthesized by a cell begins the same way: with a methionine residue, positioned by a single codon — ATG — that serves simultaneously as 'amino acid' and 'begin here.'"
ATG: The Universal Start Signal
Of all the remarkable things about methionine, one stands above the rest: its codon, ATG, is the universal start signal for protein synthesis in virtually all life on Earth. When a ribosome — the molecular machine that builds proteins — encounters an mRNA molecule and begins scanning it, it looks for one thing above all: the sequence ATG. When it finds it, protein synthesis begins. The first amino acid to be incorporated is always methionine.
🚦 How the START Codon Works
Every messenger RNA (mRNA) has a sequence called the 5' untranslated region before the protein-coding area begins. The ribosome scans along this region until it encounters the sequence AUG (the RNA version of ATG). This triggers assembly of the full ribosome and insertion of the first methionine. What follows — the rest of the protein — is entirely determined by what comes after that AUG. But without it, nothing begins.
This means that at the very beginning of its life, every protein has a methionine at its N-terminus (the starting end). In many cases, the cell removes this initial methionine afterwards through a process called N-terminal methionine excision — the protein doesn't need it for its function. But the methionine was still there, essential for getting things started.
Sulfur: The Element That Sets Methionine Apart
Methionine is one of only two amino acids in the standard set that contain sulfur (the other is cysteine). The sulfur atom in methionine is part of a thioether group — CH₃–S–CH₂– — buried in its side chain. This gives methionine its characteristic smell: the compound dimethyl sulfide, which forms when methionine is metabolized, contributes to the aroma of cooked cabbage, seaweed, and some cheeses.
Sulfur chemistry is also the reason Brazil nuts have an unusual nutritional profile. Brazil nuts are extraordinarily high in both methionine and the trace mineral selenium. A single Brazil nut can provide more than the daily requirement for selenium — largely because of the sulfur-selenium chemistry in the proteins of this remarkable Amazonian tree.
Interesting Facts
Where to Find Methionine in Food
Methionine is an essential amino acid — the human body cannot synthesize it. It must come from food. It is particularly abundant in animal proteins and some seeds:
