PMID- 16298295 OWN - NLM STAT- MEDLINE DCOM- 20060302 LR - 20071114 IS - 1074-5521 (Print) IS - 1074-5521 (Linking) VI - 12 IP - 11 DP - 2005 Nov TI - Investigating beta-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins. PG - 1163-8 AB - 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. FAU - Haltli, Brad AU - Haltli B AD - Natural Products Discovery, Wyeth Research, Pearl River, New York 10965, USA. haltlib@wyeth.com FAU - Tan, Ying AU - Tan Y FAU - Magarvey, Nathan A AU - Magarvey NA FAU - Wagenaar, Melissa AU - Wagenaar M FAU - Yin, Xihou AU - Yin X FAU - Greenstein, Michael AU - Greenstein M FAU - Hucul, John A AU - Hucul JA FAU - Zabriskie, T Mark AU - Zabriskie TM LA - eng GR - GM69320/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Chem Biol JT - Chemistry & biology JID - 9500160 RN - 0 (Amino Acids) RN - 0 (Glycopeptides) RN - 0 (Imidazolidines) RN - 0 (beta-hydroxyenduracididine) RN - 0 (mannopeptimycin) SB - IM MH - Amino Acids/*chemistry/*metabolism MH - Glycopeptides/*biosynthesis/chemistry MH - Imidazolidines/*chemistry/*metabolism MH - Mass Spectrometry MH - Molecular Sequence Data MH - Molecular Structure MH - Mutation/genetics MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Streptomyces/chemistry/*enzymology/genetics/metabolism EDAT- 2005/11/22 09:00 MHDA- 2006/03/03 09:00 CRDT- 2005/11/22 09:00 PHST- 2005/05/31 00:00 [received] PHST- 2005/09/01 00:00 [revised] PHST- 2005/09/21 00:00 [accepted] PHST- 2005/11/22 09:00 [pubmed] PHST- 2006/03/03 09:00 [medline] PHST- 2005/11/22 09:00 [entrez] AID - S1074-5521(05)00307-8 [pii] AID - 10.1016/j.chembiol.2005.09.013 [doi] PST - ppublish SO - Chem Biol. 2005 Nov;12(11):1163-8. doi: 10.1016/j.chembiol.2005.09.013.