Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics

Wan-Hong Wen; Yue Zhang; Ying-Ying Zhang; Qian Yu; Chu-Chu Jiang; Man-Cheng Tang; Jin-Yue Pu; Lian Wu; Yi-Lei Zhao; Ting Shi; Jiahai Zhou; Gong-Li Tang

doi:10.1038/s41467-021-27404-3

Nature Communications (Dec 2021)

Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics

Wan-Hong Wen,
Yue Zhang,
Ying-Ying Zhang,
Qian Yu,
Chu-Chu Jiang,
Man-Cheng Tang,
Jin-Yue Pu,
Lian Wu,
Yi-Lei Zhao,
Ting Shi,
Jiahai Zhou,
Gong-Li Tang

Affiliations

Wan-Hong Wen: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yue Zhang: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Ying-Ying Zhang: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Qian Yu: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Chu-Chu Jiang: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Man-Cheng Tang: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Jin-Yue Pu: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Lian Wu: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yi-Lei Zhao: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Ting Shi: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Jiahai Zhou: CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
Gong-Li Tang: State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences

DOI: https://doi.org/10.1038/s41467-021-27404-3
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 11

Abstract

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Antibiotic-producing organisms need to co-evolve self-protection mechanisms to avoid any damage to themselves caused by the antibiotic pharmacophore (the reactive part of the compound). In this study, the authors report a self-defense strategy in naphthyridinomycin (NDM)-producing Streptomyces lusitanus, that comprises reductive inactivation of the hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and HomW.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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