Biosynthesis of vitamin B12: mechanistic studies on the transfer of a methyl group from C-11 to C-12 and incorporation of 18O

Li, Yongfu; Alanine, Alex I.D.; Vishwakarma, Ram A.; Balachandran, Sarala; Leeper, Finian J.; Battersby, Alan R.

doi:10.1039/c39940002507

Cited by 22 publications

(20 citation statements)

References 12 publications

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“…14 Similarly, a [1,5] mutase (CobH, EC 5.4.99.61) has been observed for the transformation of precorrin-8x into hydrogenobyrinic acid, an advanced intermediate in the biosynthesis of vitamin B 12 . 15,16 Within pericyclic lyases, the conversion of isochorismate into salicylate and pyruvate through a oxa-ene reaction catalyzed by isochorismate pyruvate lyase (EC 4.2.99.21) has been reported. 17,18 As far as enzymes involved in cycloadditions are concerned, Diels−Alderase activity 19 has been proposed for several enzymes 19−23 involved in the biosynthesis of secondary metabolites in which there is an intermediate step associated with a (4 + 2) cycloaddition.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovering Biomolecules with Huisgenase Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

et al. 2019

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Designed repeat proteins catalyze the 1,3-dipolar reaction between an imine and a π-deficient dipolarophile in THF solution to form unnatural nitroproline esters, a reaction that no enzyme can catalyze. NMR studies and mutation experiments show that both acidic and basic residues can catalyze the reaction. The diastereocontrol of the reaction depends on the flexibility of the protein and on the number and location of the active lysine and glutamate residues, which can participate independently or forming dyads that promote the formation of unusual diastereomeric cycloadducts. QM/MM calculations permit one to rationalize the origins of this Huisgenase activity and of its diastereocontrol.

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Section: ■ Introductionmentioning

confidence: 99%

Discovering Biomolecules with Huisgenase Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

et al. 2019

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“…These have been used as reconstituted multi-enzyme systems which are reasonably stable to biosynthesize, on what for this area is a large scale, complex intermediates involved in the biosynthesis of vitamin B "# . The methods described have proved invaluable for the preparation of non-labelled [46,47] and specifically labelled [44,45,[48][49][50] substrates for experiments that have led to important discoveries about the way the essential vitamin B "# is synthesized in living organisms [1,2].…”

Section: Resultsmentioning

confidence: 99%

Biosynthesis of vitamin B12: the preparative multi-enzyme synthesis of precorrin-3A and 20-methylsirohydrochlorin (a 2,7,20-trimethylisobacteriochlorin)

Stamford

Crouzet²,

Cameron³

et al. 1996

Biochemical Journal

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The Bacillus subtilis genes hemB, hemC and hemD, encoding respectively the enzymes porphobilinogen synthase, hydroxymethylbilane synthase and uroporphyrinogen III synthase, have been expressed in Escherichia coli using a single plasmid construct. An enzyme preparation from this source converts 5-aminolaevulinic acid (ALA) preparatively and in high yield into uroporphyrinogen III. The Pseudomonas denitrificans genes cobA and cobI, encoding respectively the enzymes S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) and S-adenosyl-L-methionine:precorrin-2 methyltransferase (SP2MT), were also expressed in E. coli. When SUMT was combined with the coupled-enzyme system that produces uroporphyrinogen III, precorrin-2 was synthesized from ALA, and when SP2MT was also added the product from the coupling of five enzymes was precorrin-3A. Both of these products are precursors of vitamin B12, and they can be used directly for biosynthetic experiments or isolated as their didehydro octamethyl esters in > 40% overall yield. The enzyme system which produces precorrin-3A is sufficiently stable to allow long incubations on a large scale, affording substantial quantities (15-20 mg) of product.

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“…Pericyclic reactions in general are extremely rare within the enzymological context despite their prevalence in synthetic applications in organic chemistry [8, 9]. Among the naturally selected enzymes, the sigmatropic rearrangements catalyzed by chorismate mutase [10–11], isochorismate pyruvate lyase [12–13], precorrin-8x methyl mutase (CobH) [14–15] and dimethylallyltryptophan synthase [16] represent the small number of such reactions described thus far.…”

Section: Do Diels-alderases Exist?mentioning

confidence: 99%

Current developments and challenges in the search for a naturally selected Diels-Alderase

Kim

Ruszczycky

Liu

2012

Current Opinion in Chemical Biology

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Only a very few examples of enzymes known to catalyze pericyclic reactions have been reported, and presently no enzyme has been demonstrated unequivocally to catalyze a Diels-Alder reaction. Nevertheless, research into secondary metabolism has led to the discovery of numerous natural products exhibiting the structural hallmarks of [4+2] cycloadditions, prompting efforts to characterize the responsible enzymatic processes. These efforts have resulted in a growing collection of enzymes believed to catalyze pericyclic [4+2] cycloaddition reactions; however, in each case the complexity of the substrates and catalytic properties of these enzymes poses significant challenges in substantiating these hypotheses. Herein we consider the principles motivating these efforts and the enzymological systems currently under investigation.

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Biosynthesis of vitamin B12: mechanistic studies on the transfer of a methyl group from C-11 to C-12 and incorporation of 18O

Cited by 22 publications

References 12 publications

Discovering Biomolecules with Huisgenase Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

Discovering Biomolecules with Huisgenase Activity: Designed Repeat Proteins as Biocatalysts for (3 + 2) Cycloadditions

Biosynthesis of vitamin B12: the preparative multi-enzyme synthesis of precorrin-3A and 20-methylsirohydrochlorin (a 2,7,20-trimethylisobacteriochlorin)

Current developments and challenges in the search for a naturally selected Diels-Alderase

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