L-proline biosynthesis in Cupriavidus basilensis 4G11

GapMind for Amino acid biosynthesis

L-proline biosynthesis in Cupriavidus basilensis 4G11

Best path

argA, argB, argC, argD, argE, cyclodeaminase

Also see fitness data for the top candidates

Rules

Overview: Proline biosynthesis in GapMind is based on MetaCyc pathways L-proline biosynthesis I from L-glutamate (link) and III via L-ornithine aminotransferase (link). GapMind also describes proline synthesis via ornithine cyclodeaminase (PMID:11489875). Pathway II from arginine (link) should perhaps be included, but is not; it is reported in nitrogen-fixing cyanobacteria and the bacteria it was reported in also have pathway I. Pathway IV is not included because it is not reported in prokaryotes (link). Also, pathway III is described in MetaCyc as occuring only in plants, but it also is reported in the archaeon Thermococcus kodakarensis (PMC5846162).

all:

proB, proA and proC
or ornithine, OAT and proC
or ornithine and cyclodeaminase
Comment: Pathway I is proBAC. Pathway II involves ornithine aminotransferase (OAT). Some methanogens synthesize proline via ornithine cyclodeaminase (PMID:11489875). Unfortunately, the cyclodeaminase has only been linked to sequence in bacteria.

ornithine:

argA, argB, argC, argD and argE
or argJ, argB, argC and argD
or lysW, argX, lysZ, lysY, lysJ and lysK
Comment: In L-arginine biosynthesis I, ornithine forms via acetylated intermediates, argA, and argE (link). In L-arginine biosynthesis II, ornithine forms via acetylated intermediates and argJ (link). In L-arginine biosynthesis IV, ornithine forms via LysW-modified intermediates (link).

17 steps (13 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
argA	N-acylglutamate synthase	RR42_RS13035	RR42_RS18020
argB	N-acylglutamate kinase	RR42_RS01125	RR42_RS05840
argC	N-acylglutamylphosphate reductase	RR42_RS01210	RR42_RS16645
argD	N-acetylornithine aminotransferase	RR42_RS16955	RR42_RS21370
argE	N-acetylornithine deacetylase	RR42_RS07840
cyclodeaminase	ornithine cyclodeaminase	RR42_RS03960	RR42_RS29670
Alternative steps:
argJ	ornithine acetyltransferase	RR42_RS18020
argX	glutamate--LysW ligase
lysJ	[LysW]-2-aminoadipate semialdehyde transaminase / [LysW]-glutamate semialdehyde transaminase	RR42_RS26240	RR42_RS21370
lysK	[LysW]-lysine hydrolase / [LysW]-ornithine hydrolase
lysW	2-aminoadipate/glutamate carrier protein
lysY	[LysW]-2-aminoadipate 6-phosphate reductase / [LysW]-glutamylphosphate reductase
lysZ	[LysW]-2-aminoadipate 6-kinase / [LysW]-glutamate kinase	RR42_RS01125
OAT	L-ornithine 5-aminotransferase	RR42_RS26240	RR42_RS26160
proA	gamma-glutamylphosphate reductase	RR42_RS17530	RR42_RS17940
proB	glutamate 5-kinase	RR42_RS17940	RR42_RS17530
proC	pyrroline-5-carboxylate reductase	RR42_RS17360

Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway

This GapMind analysis is from Aug 03 2021. The underlying query database was built on Aug 03 2021.

Downloads

Candidates (tab-delimited)
Steps (tab-delimited)
Rules (tab-delimited)
Protein sequences (fasta format)
Organisms (tab-delimited)
SQLite3 databases

Related tools

About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code, or see changes to Amino acid biosynthesis since the publication.

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for Amino acid biosynthesis