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Synthesis of functionalized 2,3-diaminopropionates and their potential for directed monobactam biosynthesis

Michael S. Lichstrahl, Lukas Kahlert, Rongfeng Li, Trevor A. Zandi, Jerry Z. Yang, Craig A. Townsend

2023Chemical Science10 citationsDOIOpen Access PDF

Abstract

assays revealed high diastereoselectivity, as well as a substrate tolerance by the terminal adenylation domain of the non-ribosomal peptide synthetase (NRPS) SulM toward the majority of synthetic analogs. Chemical complementation of this mutant yielded a fluorinated, bioactive monobactam through fermentation as confirmed by a combination of spectrometric data and microbiological assays. This study demonstrates site-specific functionalization of a clinically important natural product and sets in place a platform for further strain improvements and engineered NRPS-biosynthesis of non-native congeners.

Topics & Concepts

BiosynthesisChemistryCombinatorial chemistryBiochemistryEnzymeCarbohydrate Chemistry and SynthesisMicrobial Natural Products and BiosynthesisChemical Synthesis and Analysis
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