A biocatalytic approach to capuramycin analogues by exploiting a substrate permissive N-transacylase CapW

Xiaodong Liu; Yuanyuan Jin; Wenlong Cai; Keith D. Green; Anwesha Goswami; Sylvie Garneau-Tsodikova; Koichi Nonaka; Satoshi Baba; Masanori Funabashi; Zhaoyong Yang; Steven G. Van Lanen

doi:10.1039/c6ob00381h

A biocatalytic approach to capuramycin analogues by exploiting a substrate permissive N-transacylase CapW

Xiaodong Liu, Yuanyuan Jin, Wenlong Cai, Keith D. Green, Anwesha Goswami, Sylvie Garneau-Tsodikova, Koichi Nonaka, Satoshi Baba, Masanori Funabashi, Zhaoyong Yang, Steven G. Van Lanen

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

12 Scopus citations

Abstract

Using the ATP-independent transacylase CapW required for the biosynthesis of capuramycin-type antibiotics, we developed a biocatalytic approach for the synthesis of 43 analogues via a one-step aminolysis reaction from a methyl ester precursor as an acyl donor and various nonnative amines as acyl acceptors. Further examination of the donor substrate scope for CapW revealed that this enzyme can also catalyze a direct transamidation reaction using the major capuramycin congener as a semisynthetic precursor. Biological activity tests revealed that a few of the new capuramycin analogues have significantly improved antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Furthermore, most of the analogues are able to be covalently modified by the phosphotransferase CapP/Cpr17 involved in self resistance, providing critical insight for future studies regarding clinical development of the capuramycin antimycobacterial antibiotics.

Original language	English
Pages (from-to)	3956-3962
Number of pages	7
Journal	Organic and Biomolecular Chemistry
Volume	14
Issue number	16
DOIs	https://doi.org/10.1039/c6ob00381h
State	Published - Apr 28 2016

Bibliographical note

Funding Information:
This work was supported by National Institute of Health grants AI087849 (S. V. L.) and UL1TR000117 (S. G.-T. and S. V. L.), a National Science Foundation CAREER award MCB 114927 (S. G-T.), and National Natural Science Foundation of China grants 81261120417, 81321004, and 81273414 (Z. Y.).

Publisher Copyright:
© The Royal Society of Chemistry 2016.

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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title = "A biocatalytic approach to capuramycin analogues by exploiting a substrate permissive N-transacylase CapW",

abstract = "Using the ATP-independent transacylase CapW required for the biosynthesis of capuramycin-type antibiotics, we developed a biocatalytic approach for the synthesis of 43 analogues via a one-step aminolysis reaction from a methyl ester precursor as an acyl donor and various nonnative amines as acyl acceptors. Further examination of the donor substrate scope for CapW revealed that this enzyme can also catalyze a direct transamidation reaction using the major capuramycin congener as a semisynthetic precursor. Biological activity tests revealed that a few of the new capuramycin analogues have significantly improved antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Furthermore, most of the analogues are able to be covalently modified by the phosphotransferase CapP/Cpr17 involved in self resistance, providing critical insight for future studies regarding clinical development of the capuramycin antimycobacterial antibiotics.",

author = "Xiaodong Liu and Yuanyuan Jin and Wenlong Cai and Green, {Keith D.} and Anwesha Goswami and Sylvie Garneau-Tsodikova and Koichi Nonaka and Satoshi Baba and Masanori Funabashi and Zhaoyong Yang and {Van Lanen}, {Steven G.}",

note = "Funding Information: This work was supported by National Institute of Health grants AI087849 (S. V. L.) and UL1TR000117 (S. G.-T. and S. V. L.), a National Science Foundation CAREER award MCB 114927 (S. G-T.), and National Natural Science Foundation of China grants 81261120417, 81321004, and 81273414 (Z. Y.). Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2016.",

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AU - Liu, Xiaodong

AU - Jin, Yuanyuan

AU - Cai, Wenlong

AU - Green, Keith D.

AU - Goswami, Anwesha

AU - Garneau-Tsodikova, Sylvie

AU - Nonaka, Koichi

AU - Baba, Satoshi

AU - Funabashi, Masanori

AU - Yang, Zhaoyong

AU - Van Lanen, Steven G.

N1 - Funding Information: This work was supported by National Institute of Health grants AI087849 (S. V. L.) and UL1TR000117 (S. G.-T. and S. V. L.), a National Science Foundation CAREER award MCB 114927 (S. G-T.), and National Natural Science Foundation of China grants 81261120417, 81321004, and 81273414 (Z. Y.). Publisher Copyright: © The Royal Society of Chemistry 2016.

PY - 2016/4/28

Y1 - 2016/4/28

N2 - Using the ATP-independent transacylase CapW required for the biosynthesis of capuramycin-type antibiotics, we developed a biocatalytic approach for the synthesis of 43 analogues via a one-step aminolysis reaction from a methyl ester precursor as an acyl donor and various nonnative amines as acyl acceptors. Further examination of the donor substrate scope for CapW revealed that this enzyme can also catalyze a direct transamidation reaction using the major capuramycin congener as a semisynthetic precursor. Biological activity tests revealed that a few of the new capuramycin analogues have significantly improved antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Furthermore, most of the analogues are able to be covalently modified by the phosphotransferase CapP/Cpr17 involved in self resistance, providing critical insight for future studies regarding clinical development of the capuramycin antimycobacterial antibiotics.

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A biocatalytic approach to capuramycin analogues by exploiting a substrate permissive N-transacylase CapW

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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