The AcbC Protein from Actinoplanes Species Is a C7-cyclitol Synthase Related to 3-Dehydroquinate Synthases and Is Involved in the Biosynthesis of the α-Glucosidase Inhibitor Acarbose

Stratmann, Ansgar; Mahmud, Taifo; Lee, Sungsook; Distler, Juergen; Floss, Heinz G.; Piepersberg, Wolfgang

doi:10.1074/jbc.274.16.10889

Cited by 69 publications

(108 citation statements)

References 36 publications

(52 reference statements)

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…Earlier work has demonstrated that 2-epi-5-epi-valiolone is the precursor of the C 7 -cyclitol unit of the acarviosyl moiety of acarbose (5,8). The expectation was that a series of enzymecatalyzed steps involving dehydration, reduction, and epimerization converted this precursor to valienol (or valienamine) before its incorporation into the pseudodisaccharide acarviosine.…”

Section: Discussionmentioning

confidence: 99%

“…Acarbose can be regarded both physiologically and structurally as a member of the aminoglycoside group of bacterial products (3)(4)(5). For instance, the three subunits of streptomycin, before condensation, are either phosphorylated (streptidine 6-phosphate) or nucleotidylated (dTDP-L-dihydrostreptose or dTDP-L-rhamnose and nucleoside diphosphate-N-methyl-Lglucosamine).…”

Section: Fig 5 Tlc Analyses Of Acbm and Acbo Assays Extracts Frommentioning

confidence: 99%

“…The techniques for all manipulations and the transformation of recombinant DNA molecules and their analysis by restriction and sequencing were performed according to standard protocols or as described earlier (5,11,15). The general strategy for cloning the acbKLMNO genes into the expression vectors indicated in Table I with an N-terminal His-tagged fusion peptide was as follows.…”

Section: Cloning Manipulation and Sequencing Of Dnamentioning

confidence: 99%

“…Its product was shown to be a C 7 -cyclitol synthase using sedo-heptulose 7-phosphate as substrate for the production of 2-epi-5-epi-valiolone (5). Until now, no other intermediate for the biosynthesis of acarbose has been identified.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Biosynthesis of the C7-cyclitol Moiety of Acarbose inActinoplanes Species SE50/110

Zhang¹,

Stratmann²,

Block³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

We have previously demonstrated that the biosynthesis of the C 7 -cyclitol, called valienol (or valienamine), of the ␣-glucosidase inhibitor acarbose starts from the cyclization of sedo-heptulose 7-phosphate to 2-epi-5-epivaliolone (Stratmann, A., Mahmud, T., Lee, S., Distler, J., Thus, a phosphotransferase activity was identified modifying 2-epi-5-epi-valiolone by ATP-dependent phosphorylation. This activity could be attributed to the AcbM protein by verifying this activity in S. lividans strain TK64/pCW4123M, expressing His-tagged AcbM. The Histagged AcbM protein was purified and subsequently characterized as a 2-epi-5-epi-valiolone 7-kinase, presumably catalyzing the first enzyme reaction in the biosynthetic route, leading to an activated form of the intermediate 1-epi-valienol. The AcbK protein could not catalyze the same reaction nor convert any of the other C 7 -cyclitol monomers tested. The 2-epi-5-epi-valiolone 7-phosphate was further converted by the AcbO protein to another isomeric and phosphorylated intermediate, which was likely to be the 2-epimer 5-epi-valiolone 7-phosphate. The products of both enzyme reactions were characterized by mass spectrometric methods. The product of the AcbM-catalyzed reaction, 2-epi-5-epi-valiolone 7-phosphate, was purified on a preparative scale and identified by NMR spectroscopy. A biosynthetic pathway for the pseudodisaccharidic acarviosyl moiety of acarbose is proposed on the basis of these data.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Fig 5 Tlc Analyses Of Acbm and Acbo Assays Extracts Frommentioning

confidence: 99%

Section: Cloning Manipulation and Sequencing Of Dnamentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Biosynthesis of the C7-cyclitol Moiety of Acarbose inActinoplanes Species SE50/110

Zhang¹,

Stratmann²,

Block³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…SE50/110 (26,27). Despite its high similarity to CGTases, it has been reported that ATase has no cyclodextrin-forming activity and is not inhibited by acarbose (14).…”

mentioning

confidence: 99%

Single Amino Acid Mutations Interchange the Reaction Specificities of Cyclodextrin Glycosyltransferase and the Acarbose-Modifying Enzyme Acarviosyl Transferase

2004

View full text Add to dashboard Cite

Single amino acid mutations interchange the reaction specificities of cyclodextrin glycosyltransferase and the acarbose-modifying enzyme acarviosyl transferase Leemhuis, H.; Wehmeier, U.F.; Dijkhuizen, Lubbert Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. D-42079 Wuppertal, Germany ReceiVed May 15, 2004; ReVised Manuscript ReceiVed July 22, 2004 ABSTRACT: Acarviosyl transferase (ATase) from Actinoplanes sp. SE50/110 is a bacterial enzyme that transfers the acarviosyl moiety of the diabetic drug acarbose to sugar acceptors. The enzyme exhibits 42% sequence identity with cyclodextrin glycosyltransferases (CGTase), and both enzymes are members of the R-amylase family, a large clan of enzymes acting on starch and related compounds. ATase is virtually inactive on starch, however. In contrast, ATase is the only known enzyme to efficiently use acarbose as substrate (2 µmol min -1 mg -1 ); acarbose is a strong inhibitor of CGTase and of most other R-amylase family enzymes. This distinct reaction specificity makes ATase an interesting enzyme to investigate the variation in reaction specificity of R-amylase family enzymes. Here we show that a G140H mutation in ATase, introducing the typical His of the conserved sequence region I of the R-amylase family, changed ATase into an enzyme with 4-R-glucanotransferase activity (3.4 µmol min -1 mg -1 ). Moreover, this mutation introduced cyclodextrin-forming activity into ATase, converting 2% of starch into cyclodextrins. The opposite experiment, removing this typical His side chain in CGTase (H140A), introduced acarviosyl transferase activity in CGTase (0.25 µmol min -1 mg -1 ).The R-amylase family, or glycoside hydrolase family 13 (1), is a large family of enzymes acting on R-glycosidic bonds in starch and related compounds (2). About 20 different reaction specificities have been identified in this family, including hydrolysis of R-(1,4)-and R-(1,6)-glycosidic linkages (e.g., R-amylase and isoamylase, respectively), as well as the formation of R-(1,4)-and R-(1,6)-glycosidic bonds (e.g., amylosucrase, acarviosyl transferase, cyclodextrin glycosyltransferase, and branching enzyme, respectively; Figure 1) (2, 3). All members use an R-retaining double displacement mechanism (4) in which reactions proceed via a covalent glycosyl-enzyme intermediate (5). Glycosidic bond cleavage occurs between subsites -1 and +1 ( Figure 2A), and after cleavage the glycosyl reaction intermediate re...

show abstract

Biosynthesis of Gabosines A, B, and C, Carba Sugars fromStreptomyces cellulosae

et al. 2000

View full text Add to dashboard Cite

The biosynthesis of the gabosines A−C (3−5) was studied by feeding cultures of Streptomyces cellulosae subsp. griseorubiginosus (strain S 1096) with 13C‐labeled precursors. Although the carba sugars are structurally related to shikimic acid, the biosynthetic origin was found to be different to the shikimate pathway. The results revealed that the gabosines are formed via a pentose phosphate pathway by cyclization of a heptulose phosphate intermediate. This intermediate arises from a triose phosphate by successive transfer of two C2 fragments by transketolases. This pathway is identical as that described for valienamine (7), the aminocarba sugar moiety of validamycin, and acarbose (2). The results from biosynthetic studies are discussed on the background of the variety of gabosines found in nature.

show abstract

The AcbC Protein from Actinoplanes Species Is a C7-cyclitol Synthase Related to 3-Dehydroquinate Synthases and Is Involved in the Biosynthesis of the α-Glucosidase Inhibitor Acarbose

Cited by 69 publications

References 36 publications

Biosynthesis of the C7-cyclitol Moiety of Acarbose inActinoplanes Species SE50/110

Biosynthesis of the C7-cyclitol Moiety of Acarbose inActinoplanes Species SE50/110

Single Amino Acid Mutations Interchange the Reaction Specificities of Cyclodextrin Glycosyltransferase and the Acarbose-Modifying Enzyme Acarviosyl Transferase

Biosynthesis of Gabosines A, B, and C, Carba Sugars fromStreptomyces cellulosae

Contact Info

Product

Resources

About