Deoxysugar Formation via 4',5'‐Dehydration on PKS Assembly Line in Nucleoside Antibiotic Biosynthesis
Abstract
ABSTRACT Amipurimycin is a peptidyl nucleoside antibiotic characterized by a C 9 high‐carbon sugar, with potent activity against the rice blast pathogen Pyricularia oryzae . The biosynthetic machinery of the C‐4' methylene group in its deoxy sugar has remained unknown. This study reveals that ApmL, a hypothetical protein in the DUF3500 family, functions as a 4′,5′‐dehydratase whose activity is strictly dependent on the PKS assembly line. Together with its partner reductase ApmM, they complete a two‐step C‐4′ deoxygenation process via dehydration‐reduction. We achieve the first in vitro reconstitution of this unique PKS‐coupled dehydration process and show direct interaction between ApmL and PKS proteins. Our findings establish ApmL as a new family of dehydratase and uncover a noncanonical deoxygenation strategy in nucleoside antibiotic biosynthesis.
Article Details
Authors (10)
Zi‐Hui Chen
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Fei Wang
Weiyan Wang
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Tian‐Ci Zhang
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Yi‐Lin Wang
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Wen‐He Zhang
State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai China
Jinyue Pu
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Aiai Sun
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Hai‐Xue Pan
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China
Gong‐Li Tang
Key Laboratory of Glyco‐drug Research of Zhejiang Province School of Chemistry and Materials Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China