SynBio-SynChem Approaches to Diversifying the Pacidamycins through the Exploitation of an Observed Pictet-Spengler Reaction
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Wiley-VCH Verlag
Abstract
A nonenzymatic Pictet-Spengler reaction has been postulated to give rise to a subset of naturally occurring uridyl peptide antibiotics (UPAs). Here, using a combination of strain engineering and synthetic chemistry, we demonstrate that Pictet-Spengler chemistry may be employed to generate even greater diversity in the UPAs. We use an engineered strain to afford access to meta-tyrosine containing pacidamycin 4. Pictet-Spengler diversification of this compound using a small series of aryl-aldehydes was achieved with some derivatives affording remarkable diastereomeric control. © 2020 The Authors. ChemBioChem published by Wiley-VCH GmbH
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Compound diversification, Natural products, Pacidamycin, Pictet-spengler, Semisynthesis, Uridyl peptide antibiotic, Anti-bacterial agents, Oligopeptides, Peptides, Streptomyces, Uridine, Pacidamycin 4, Polypeptide antibiotic agent, Tetrahydroisoquinoline, Unclassified drug, Antiinfective agent, Oligopeptide, Peptide, Amino terminal sequence, Article, Bacterial strain, Bacterium culture, Diastereoisomer, Diastereoselectivity, Drug synthesis, Fermentation, Gene, Gene cluster, Gene control, Horizontal gene transfer, Ion exchange, Liquid chromatography-mass spectrometry, Mic90, Nonhuman, Npsm gene, Nuclear magnetic resonance spectroscopy, Pictet spengler reaction, Plasmid, Priority journal, Proton nuclear magnetic resonance, Pseudomonas aeruginosa, Reversed phase liquid chromatography, Streptomyces coeruleorubidus, Metabolism, Synthesis