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:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Cobalamin Biosynthesis → Aminopropanol Phosphate Biosynthesis|
Expected Taxonomic Range:
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 126.96.36.199, L-threonine 3-dehydrogenase and EC 188.8.131.52, (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 184.108.40.206, 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 220.127.116.11, 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.
Variants: aminopropanol phosphate biosynthesis II
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
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
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
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
©2016 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493