Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis

I. Hsuan Chen; Ting Cheng; Yung Lin Wang; Szu Jo Huang; Yu Hsuan Hsiao; Yi Ting Lai; Shu Ing Toh; John Chu; Jeffrey D. Rudolf; Chin Yuan Chang

doi:10.1002/cbic.202200563

Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis

I. Hsuan Chen, Ting Cheng, Yung Lin Wang, Szu Jo Huang, Yu Hsuan Hsiao, Yi Ting Lai, Shu Ing Toh, John Chu, Jeffrey D. Rudolf, Chin Yuan Chang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l-Arg to form l-Cap. l-Cap is then adenylated by CmnG-A before being incorporated into the nonribosomal peptide. The co-crystal structures of CmnG-A with l-Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.

Original language	English
Article number	e202200563
Journal	ChemBioChem
Volume	23
Issue number	24
DOIs	https://doi.org/10.1002/cbic.202200563
State	Published - 16 Dec 2022

Keywords

CmnG
adenylation domains
capreomycidine
capreomycin
nonproteinogenic amino acid

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10.1002/cbic.202200563

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Chen, I. H., Cheng, T., Wang, Y. L., Huang, S. J., Hsiao, Y. H., Lai, Y. T., Toh, S. I., Chu, J., Rudolf, J. D., & Chang, C. Y. (2022). Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis. ChemBioChem, 23(24), Article e202200563. https://doi.org/10.1002/cbic.202200563

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title = "Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis",

abstract = "Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l-Arg to form l-Cap. l-Cap is then adenylated by CmnG-A before being incorporated into the nonribosomal peptide. The co-crystal structures of CmnG-A with l-Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.",

keywords = "CmnG, adenylation domains, capreomycidine, capreomycin, nonproteinogenic amino acid",

author = "Chen, {I. Hsuan} and Ting Cheng and Wang, {Yung Lin} and Huang, {Szu Jo} and Hsiao, {Yu Hsuan} and Lai, {Yi Ting} and Toh, {Shu Ing} and John Chu and Rudolf, {Jeffrey D.} and Chang, {Chin Yuan}",

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year = "2022",

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day = "16",

doi = "10.1002/cbic.202200563",

language = "English",

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T1 - Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis

AU - Chen, I. Hsuan

AU - Cheng, Ting

AU - Wang, Yung Lin

AU - Huang, Szu Jo

AU - Hsiao, Yu Hsuan

AU - Lai, Yi Ting

AU - Toh, Shu Ing

AU - Chu, John

AU - Rudolf, Jeffrey D.

AU - Chang, Chin Yuan

PY - 2022/12/16

Y1 - 2022/12/16

N2 - Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l-Arg to form l-Cap. l-Cap is then adenylated by CmnG-A before being incorporated into the nonribosomal peptide. The co-crystal structures of CmnG-A with l-Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.

AB - Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l-Arg to form l-Cap. l-Cap is then adenylated by CmnG-A before being incorporated into the nonribosomal peptide. The co-crystal structures of CmnG-A with l-Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.

KW - CmnG

KW - adenylation domains

KW - capreomycidine

KW - capreomycin

KW - nonproteinogenic amino acid

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U2 - 10.1002/cbic.202200563

DO - 10.1002/cbic.202200563

M3 - Article

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AN - SCOPUS:85142036118

SN - 1439-4227

VL - 23

JO - ChemBioChem

JF - ChemBioChem

IS - 24

M1 - e202200563

ER -

Characterization and Structural Determination of CmnG-A, the Adenylation Domain That Activates the Nonproteinogenic Amino Acid Capreomycidine in Capreomycin Biosynthesis

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