MetaCyc L-lysine biosynthesis I

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Some taxa known to possess this pathway include : Arthrobacter globiformis, Azotobacter vinelandii, Bordetella pertussis, Corynebacterium glutamicum, Corynebacterium glutamicum ATCC 13032, Escherichia coli K-12 substr. MG1655, Haemophilus influenzae, Haemophilus influenzae Rd KW20, Helicobacter pylori, Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv, Rhodospirillum rubrum

Expected Taxonomic Range: Bacteria <bacteria>

Synonyms: L-lysine and L-diaminopimelate biosynthesis

BioCyc ID: DAPLYSINESYN-PWY

Superclasses:

Biosynthesis → Amino Acid Biosynthesis → Proteinogenic Amino Acid Biosynthesis → L-lysine Biosynthesis

Summary:
General Background

Six pathways are now recognized in bacteria, most algae, fungi and higher plants for the biosynthesis of lysine. They are divided into two groups - the diaminopimelate (DAP) pathways, and the L-2-aminoadipate pathways.

In the pathways that belong to the DAP group, lysine is produced from aspartate (along with methionine, threonine and isoleucine). All of the DAP group pathways share the upper segments, which include the four steps required for conversion of L-aspartate to (S)-2,3,4,5-tetrahydrodipicolinate. They also share the last step, which is the conversion of the intermediate meso-diaminopimelate (D,L-DAP, or meso-DAP) to lysine. However, these pathways differ in the routes leading from (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate. The four variations include:

(I) the succinylase variant (see L-lysine biosynthesis I), which involves succinylated intermediates. In this route (S)-2,3,4,5-tetrahydrodipicolinate is coverted to meso-diaminopimelate in four enzymatic steps.

(II) the acetylase variant (see L-lysine biosynthesis II), which involves acetylated intermediates. This route also involves four enzymatic steps for the conversion of (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate.

(III) the dehydrogenase variant (see L-lysine biosynthesis III), in which (S)-2,3,4,5-tetrahydrodipicolinate is converted to meso-diaminopimelate in a single enzymatic step.

(IV) the diaminopimelate-aminotransferase variant (see L-lysine biosynthesis VI), in which (S)-2,3,4,5-tetrahydrodipicolinate is converted to meso-diaminopimelate in two steps.

In addition to lysine, all of the pathways in this group also produce meso-diaminopimelate, which is an important metabolite on its own (for example, as a constituent of bacterial cell wall peptidoglycan).

The two other pathways belong to the L-2-aminoadipate group. They are found in organisms that have no requirement for meso-diaminopimelate, as it is not a component of their cell walls. These pathways also share the first segments, leading to the synthesis of the intermediate L-2-aminoadipate (α-aminoadipate). However, in yeast and fungi, as well as Euglena, the pathway continues with the key enzyme L-2-aminoadipate reductase, leading to the intermediate L-saccharopine (see L-lysine biosynthesis IV), while in prokaryotes the pathway continues in a path similar to bacterial arginine biosynthesis (see L-lysine biosynthesis V).

Most of the bacteria that have been investigated in detail appear to utilize only one of these pathways [Schrumpf91]. A few exceptions include Paenibacillus macerans, in which variants (II) and (III) seem to coexist [Bartlett85], and Corynebacterium glutamicum, in which variant (I) and (III) coexist [Schrumpf91].

Lysine is one of the 10 essential amino acids that mammals are unable to synthesize, and must therefore acquire in their diets.

About This Pathway

The succinylase variant is the most common bacterial lysine biosynthesis pathway. It is found in many different types of bacteria. In this pathway, a succinate moiety is added to (S)-2,3,4,5-tetrahydrodipicolinate, followed by an amino group, to form N-succinyl-L,L-DAP. The succinate is then removed, and an epimerase converts the resulting L,L-DAP to meso-DAP. This pathway has been experimentally verified in several Gram-negative bacteria, including Escherichia coli K-12, Haemophilus influenzae Rd KW20, Corynebacterium glutamicum, Helicobacter pylori and Mycobacterium tuberculosis, and genes specific for this pathway have been identified in many other organisms.