Characterization of Miharamycin Biosynthesis Reveals a Hybrid NRPS–PKS to Synthesize High-Carbon Sugar from a Complex Nucleoside
Fei Wang, Wen-He Zhang, Juan Zhao, Wenjia Kang, Shengyang Wang, Biao Yu, Hai‐Xue Pan, Gong‐Li Tang
Abstract
Miharamycins are peptidyl nucleoside antibiotics with a unique branched C9 pyranosyl amino acid core and a rare 2-aminopurine moiety. Inactivation of 19 genes in the biosynthetic gene cluster and identification of several unexpected intermediates suggest an alternative biosynthetic pathway, which is further supported by feeding experiments and in vitro characterization of an unusual adenylation domain recognizing a complex nucleoside derivative as the substrate. These results thereby provide an unprecedented biosynthetic route of high-carbon sugar catalyzed by atypical hybrid nonribosomal peptide synthetase–polyketide synthase.
Topics & Concepts
ChemistrySugarBiosynthesisNucleosideCharacterization (materials science)Carbon fibersStereochemistryBiochemistryGeneNanotechnologyComposite materialMaterials scienceComposite numberCarbohydrate Chemistry and SynthesisPlant Disease Resistance and GeneticsBiochemical and Molecular Research