A heteromeric cis-prenyltransferase is responsible for the biosynthesis of glycosyl carrier lipids in Methanosarcina mazei

Emi, Koh-ichi; Sompiyachoke, Kitty; Okada, Miyako; Hemmi, Hisashi

doi:10.1016/j.bbrc.2019.09.143

Cited by 12 publications

(16 citation statements)

References 25 publications

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“…5 B ). The atom positions, however, are inconsistent with the substrate preference of MM_0014, where IPP is much more reactive than DMAPP as the prenyl acceptor ( 13 ). In fact, the position of IPP seems unsuitable for the reaction.…”

Section: Resultsmentioning

confidence: 97%

“…S4 ). This difference in distance could be why MM_0014 cannot catalyze the head-to-middle condensation between two DMAPP molecules, while it can catalyze the head-to-tail condensation between DMAPP and IPP ( 13 ). Although the IPP-binding structure of MM_0014 (free+IPP) did not provide verifiable information about distance, we inferred the cause for the substrate specificity of MM_0014 toward IPP based on the DMAPP-binding structure, as described above.…”

Section: Discussionmentioning

confidence: 99%

“…The physiological role of MM_0014 remains unclear. Regular prenyl condensation reactions catalyzed by the enzyme from prenyl pyrophosphates and IPP yield C 25–40 polyprenyl pyrophosphates that are shorter than the C 50 polyprenyl chain of the putative glycosyl carrier lipid extracted from M. mazei cells ( 13 ). Because the other cPT paralogs from M. mazei , MM_0618 and MM_1083, are known to form heteromeric cPT and are used to synthesize C 45–50 products, they are likely responsible for glycosyl carrier lipid biosynthesis ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, some cPTs are known to catalyze both head-to-tail and head-to-middle prenyl condensation reactions. MA1831 and MM_0014, which are orthologous cPTs from the methanogenic archaea Methanosarcina acetivorans and Methanosarcina mazei , respectively, unusually accept both IPP and DMAPP as prenyl acceptor substrates ( 13 , 14 ). The regular condensation reaction between FPP and IPP gives relatively short polyprenyl pyrophosphates, while the irregular reaction between FPP and DMAPP yields geranyllavandulyl pyrophosphate ( Fig.…”

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confidence: 99%

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A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations

Okada

Unno

Emi

et al. 2021

Journal of Biological Chemistry

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Polyprenyl groups, products of isoprenoid metabolism, are utilized in peptidoglycan biosynthesis, protein N -glycosylation, and other processes. These groups are formed by cis -prenyltransferases, which use allylic prenyl pyrophosphates as prenyl-donors to catalyze the C -prenylation of the general acceptor substrate, isopentenyl pyrophosphate. Repetition of this reaction forms ( Z,E -mixed)-polyprenyl pyrophosphates, which are converted later into glycosyl carrier lipids, such as undecaprenyl phosphate and dolichyl phosphate. MM_0014 from the methanogenic archaeon Methanosarcina mazei is known as a versatile cis -prenyltransferase that accepts both isopentenyl pyrophosphate and dimethylallyl pyrophosphate as acceptor substrates. To learn more about this enzyme’s catalytic activity, we determined the X-ray crystal structures of MM_0014 in the presence or absence of these substrates. Surprisingly, one structure revealed a complex with O -prenylglycerol, suggesting that the enzyme catalyzed the prenylation of glycerol contained in the crystallization buffer. Further analyses confirmed that the enzyme could catalyze the O -prenylation of small alcohols, such as 2-propanol, expanding our understanding of the catalytic ability of cis -prenyltransferases.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations

Okada

Unno

Emi

et al. 2021

Journal of Biological Chemistry

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“…As the product standards for co-spot TLC analysis, alcohol products of unlabeled E-C 10-20 and E-C 45 were commercially available, and unlabeled E-C 25-35 and Z-C 15 were previously synthesized. [6,26,27] C 50-60 polyprenol mixture, which were identified by LC-ESI-MS [28] was provided by Dr. Hisashi Hemmi (Nagoya University). Unlabeled polyprenols were detected with iodine vapor.…”

Section: Product Analyses Of Idssmentioning

confidence: 99%

Insight into Isoprenoid Biosynthesis by Functional Analysis of Isoprenyl Diphosphate Synthases from Mycobacterium vanbaalenii and Mycobacterium tuberculosis

et al. 2020

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Comprehensive functional analyses of E-isoprenyl diphosphate synthases (E-IDSs) from nonpathogenic Mycobacterium vanbaalenii have been performed. Mv0992 and Mv1577 represent a nonaprenyl diphosphate (E-C 45) synthase and a geranylgeranyl diphosphate (E-C 20) synthase, respectively. Although Mv3536 was identified as an E-C 20 synthase using a single enzyme, coincubation of Mv3536 and Z-IDSs (Mv4662 and Mv3822) strongly suggested it releases an intermediate geranyl diphosphate (E-C 10) during a continuous condensation reaction. Mv0992 and Mv3536 functions differed from those of the previously reported pathogenic Mycobacterium tuberculosis homologues Rv0562 and Rv2173, respectively. Re-analysis of Rv0562 and Rv2173 demonstrated that their functions were similar to those of Mv0992 and Mv3536 (Rv0562: E-C 45 synthase; Rv2173: E-C 10-15 synthase). The newly proposed functions of Rv0562 and Rv2173 would be in the biosynthesis of menaquinone and glycosyl carrier lipids essential for growth. Furthermore, a reduced allylic diphosphate could be used as the Z-IDS of the Mv3822 substrate, thereby introducing a potentially novel pathway of cyclic sesquarterpene biosynthesis.

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Engineering of a Plant Isoprenyl Diphosphate Synthase for Development of Irregular Coupling Activity

Gerasymenko

Sheludko

Navarro³

et al. 2021

ChemBioChem

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A heteromeric cis-prenyltransferase is responsible for the biosynthesis of glycosyl carrier lipids in Methanosarcina mazei

Cited by 12 publications

References 25 publications

A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations

A versatile cis-prenyltransferase from Methanosarcina mazei catalyzes both C- and O-prenylations

Insight into Isoprenoid Biosynthesis by Functional Analysis of Isoprenyl Diphosphate Synthases from Mycobacterium vanbaalenii and Mycobacterium tuberculosis

Engineering of a Plant Isoprenyl Diphosphate Synthase for Development of Irregular Coupling Activity

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