Deoxysugar Formation via 4',5'-Dehydration on PKS Assembly Line in Nucleoside Antibiotic Biosynthesis
Zi-Hui Chen1, Fei Wang2, Weiyan Wang1
1Key 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.
None:
Amipurimycin is a peptidyl nucleoside antibiotic characterized by a C9 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.
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