As an essential amino acid, methionine is not synthesized de novo in humans and other animals, which must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine biosynthesis belongs to the aspartate family, along with threonine and lysine (via diaminopimelate, but not via α-aminoadipate). The main backbone is derived from aspartic acid, while the sulfur may come from cysteine, methanethiol, or hydrogen sulfide.

1. BIOSYNTHESIS OF
METHIONINE
RANA SAHA
B.PHARM. - NSHM KNOWLEDGE CAMPUS, KOLKATA

2. INTRODUCTION:
L-methionine (Met) is one of the proteinogenic amino acids. In
addition to its role in protein biosynthesis, L-methionine is
required for a number of important cellular functions,
including the initiation of protein synthesis, the methylation of
DNA, rRNA and xenobiotics, and the biosynthesis of cysteine,
phospholipids and polyamines.

3. BIOSYNTHESIS :
Some bacteria can synthesize methionine using organic sulfur through transsulfuration
of O-succinyl-L-homoserine with L-cysteine to form L-cystathionine. Cystathionine is
then cleaved to L-homocysteine, which is methylated to methionine . Plants use a
modification of this pathway, where O-phospho-L-homoserine, instead of O-succinyl-L-
homoserine, is the intermediate converting homoserine to cystathionine.
Other bacteria, as well as yeast and fungi, can use a different route in which they
directly assimilate inorganic sulfur by a sulfhydrylation . In that route hydrogen sulfide,
the final product of microbial sulfate reduction reacts with O-acetylated homoserine,
with replacement of the acetyl group by sulfide to form L-homocysteine, which is once
again methylated to methionine .

4. Most methanogenic archaea utilize yet a different pathway. While these organisms also
use hydrogen sulfide as the sulfur source, the other precursor for L-homocysteine
production is L-aspartate-semialdehyde, produced from L-aspartate .
Methylation of L-homocysteine is catalyzed by either a cobalamin-independent
enzyme ( EC 2.1.1.13) or a cobalamin-dependent enzyme ( EC 2.1.1.14), depending upon
the species or growth conditions.
While many organisms seem to contain both routes for methionine biosynthesis, in
Escherichia coli and other enteric bacteria only the transsulfuration pathway is used
complementation of known mutants; analysis of mutant phenotypes; and gene cloning,
expression, and enzyme activity assays. The presence of EC 2.5.1.49, O-
acetylhomoserine aminocarboxypropyltransferase was considered indicative of the
presence of a direct sulfhydrylation pathway. Note that all bacterial methionine
biosynthetic pathways involve acylated homoserine.

6.  Enzymes involved in the E. coli trans-sulfurylation route of methionine
biosynthesis:
 Aspartokinase
 Aspartate-semialdehyde dehydrogenase
 Homoserine dehydrogenase
 Homoserine O-transsuccinylase
 Cystathionine-γ-synthase
 Cystathionine-β-lyase
 Methionine synthase (in mammals, this step is performed by homocysteine
methyltransferase or betaine—homocysteine S-methyltransferase.)