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MetaCyc Pathway: aminopropanol phosphate biosynthesis I
Inferred from experiment

Enzyme View:

Pathway diagram: aminopropanol phosphate 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.

Synonyms: 1-amino-propan-2-yl phosphate biosynthesis from threonine, (R)-1-amino-2-propanol O-2-phosphate biosynthesis

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisVitamins BiosynthesisCobalamin BiosynthesisAminopropanol Phosphate Biosynthesis

Some taxa known to possess this pathway include : Pseudomonas denitrificans, Salmonella enterica enterica serovar Typhimurium

Expected Taxonomic Range: Bacteria

The biosynthesis of adenosylcobinamide from adenosylcobyrate requires the attachment of an aminopropanol group to the propionate side chain of the corrin ring. Isotope studies with cultures of microorganisms that biosynthesize vitamin B12 have clearly shown that the amino group and carbon chain of this part of cobalamin are both derived from L-threonine [Krasna57].

Initial work suggested that (R)-1-aminopropan-2-ol might be formed from L-threonine by sequential action of two separate enzymes, namely EC, L-threonine 3-dehydrogenase and EC, (R)-aminopropanol dehydrogenase [Campbell73] (see aminopropanol phosphate biosynthesis II). These two enzymes have been purified from Escherichia coli K-12 and were shown to catalyze the proposed reactions in vitro [Campbell78]. At the time it was proposed that (R)-1-aminopropan-2-ol is the substrate for the CbiB enzyme, originally proposed to convert adenosylcobyrate to adenosylcobinamide [Brushaber98].

Suprisingly, a few years later a Salmonella enterica enterica serovar Typhimurium mutant blocked in (R)-1-aminopropan-2-ol biosynthesis was found to be not defective in either of these two enzymes. Furthermore, the researchers could demonstrate that blocking the two enzymes does not effect B12 biosynthesis in this organism [Grabau92]. The mutation responsible for the phenotype was eventually traced to EC, threonine-phosphate decarboxylase ( cobD). This enzyme does not accept L-threonine as a substrate, and is specific to L-threonine 3-O-phosphate. The authors suggested that the product of this reaction, (R)-1-amino-2-propanol O-2-phosphate, is the actual substrate for the CbiB enzyme, originally proposed to convert adenosylcobyrate to adenosylcobinamide [Brushaber98].

The evidence for this proposed pathway was strengthened by the discovery of EC, L-threonine kinase ( pduX) in Salmonella enterica enterica serovar Typhimurium. This enzyme generates L-threonine 3-O-phosphate from L-threonine [Fan08]. Growth studies showed that pduX mutants were impaired for the synthesis of adenosylcobalamin de novo and from cobyrate, but not from cobinamide [Fan08].

It should be noted that homologs of pduX were only found in some proteobacteria, actinobacteria, and firmicutes. It is still not clear whether a different enzyme catalyzes the phosphorylation of L-threonine in other cobalamin-producing bacteria, or whether other pathway variants exist for aminopropanol phosphate biosynthesis in those organisms.

Superpathways: superpathway of L-threonine metabolism, adenosylcobalamin biosynthesis II (aerobic), adenosylcobalamin biosynthesis I (anaerobic)

Variants: aminopropanol phosphate biosynthesis II

Created 08-Jan-2007 by Caspi R, SRI International
Revised 25-Sep-2013 by Caspi R, SRI International


Brushaber98: Brushaber KR, O'Toole GA, Escalante-Semerena JC (1998). "CobD, a novel enzyme with L-threonine-O-3-phosphate decarboxylase activity, is responsible for the synthesis of (R)-1-amino-2-propanol O-2-phosphate, a proposed new intermediate in cobalamin biosynthesis in Salmonella typhimurium LT2." J Biol Chem 273(5);2684-91. PMID: 9446573

Campbell73: Campbell RL, Dekker EE (1973). "Formation of D-1-amino-2-propanol from L-threonine by enzymes from Escherichia coli K-12." Biochem Biophys Res Commun 53(2);432-8. PMID: 4577583

Campbell78: Campbell RL, Swain RR, Dekker EE (1978). "Purification, separation, and characterization of two molecular forms of D-1-amino-2-propanol:NAD+ oxidoreductase activity from extracts of Escherichia coli K-12." J Biol Chem 253(20);7282-8. PMID: 359547

Fan08: Fan C, Bobik TA (2008). "The PDUX enzyme of salmonella enterica is an L-threonine kinase used for coenzyme B12 synthesis." J Biol Chem. PMID: 18308727

Grabau92: Grabau C, Roth JR (1992). "A Salmonella typhimurium cobalamin-deficient mutant blocked in 1-amino-2-propanol synthesis." J Bacteriol 174(7);2138-44. PMID: 1551838

Krasna57: Krasna AI, Rosenblum C, Sprinson DB (1957). "The conversion of L-threonine to the Dg-1-amino-2-propanol of vitamin B12." J Biol Chem 225(2);745-50. PMID: 13416277

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Blanche95: Blanche F., Cameron B., Crouzet J., Debussche L., Thibaut D., Vuilhorgne M., Leeper F. J., Battersby A. R. (1995). "Vitamin B12: how the problem of its biosynthesis was solved." Angewandte Chemie. International edition in English 34(4): 383-411.

Cheong02: Cheong CG, Bauer CB, Brushaber KR, Escalante-Semerena JC, Rayment I (2002). "Three-dimensional structure of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica." Biochemistry 41(15);4798-808. PMID: 11939774

Cheong02a: Cheong CG, Escalante-Semerena JC, Rayment I (2002). "Structural studies of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica: the apo, substrate, and product-aldimine complexes." Biochemistry 41(29);9079-89. PMID: 12119022

Crouzet90: Crouzet J, Cauchois L, Blanche F, Debussche L, Thibaut D, Rouyez MC, Rigault S, Mayaux JF, Cameron B (1990). "Nucleotide sequence of a Pseudomonas denitrificans 5.4-kilobase DNA fragment containing five cob genes and identification of structural genes encoding S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase and cobyrinic acid a,c-diamide synthase." J Bacteriol 172(10);5968-79. PMID: 2211520

Fan09: Fan C, Fromm HJ, Bobik TA (2009). "Kinetic and functional analysis of L-threonine kinase, the PduX enzyme of Salmonella enterica." J Biol Chem 284(30);20240-8. PMID: 19509296

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Rodionov03: Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS (2003). "Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes." J Biol Chem 278(42);41148-59. PMID: 12869542

Thomas00: Thomas MG, Escalante-Semerena JC (2000). "Identification of an alternative nucleoside triphosphate: 5'-deoxyadenosylcobinamide phosphate nucleotidyltransferase in Methanobacterium thermoautotrophicum delta H." J Bacteriol 182(15);4227-33. PMID: 10894731

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Fri Apr 29, 2016, biocyc11.