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Updated: Aug 14, 2026

Production and Testing of Antimicrobial Peptides and Their Mimics
Published on: April 10, 2026
Investigating beta-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins
Brad Haltli1, Ying Tan, Nathan A Magarvey
1Natural Products Discovery, Wyeth Research, Pearl River, New York 10965, USA. haltlib@wyeth.com
Abstract:
The mannopeptimycins (MPPs) are potent glycopeptide antibiotics that contain both D and L forms of the unique, arginine-derived amino acid beta-hydroxyenduracididine (betahEnd). The product of the mppO gene in the MPP biosynthetic cluster resembles several non-heme iron, alpha-ketoglutarate-dependent oxygenases, such as VioC and clavaminate synthase. The role of MppO in betahEnd biosynthesis was confirmed through inactivation of mppO, which yielded a strain that produced dideoxy-MPPs, indicating that mppO is essential for generating the beta-hydroxy functionality for both betahEnd residues. Characterization in vitro of recombinant His6-MppO expressed in E. coli revealed that MppO selectively hydroxylates the beta carbon of free L-enduracididine.
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