PMID- 22222159
OWN - NLM
STAT- MEDLINE
DCOM- 20120511
LR  - 20211021
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 20
IP  - 2
DP  - 2012 Jan 15
TI  - Studies on the biosynthesis of the lipodepsipeptide antibiotic Ramoplanin A2.
PG  - 859-65
LID - 10.1016/j.bmc.2011.11.062 [doi]
AB  - Ramoplanin, a non-ribosomally synthesized peptide antibiotic, is highly effective 
      against several drug-resistant Gram-positive bacteria, including 
      vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant 
      Staphylococcus aureus (MRSA), two important opportunistic human pathogens. 
      Recently, the biosynthetic cluster from the ramoplanin producer Actinoplanes ATCC 
      33076 was sequenced, revealing an unusual architecture of fatty acid and 
      non-ribosomal peptide synthetase biosynthetic genes (NRPSs). The first steps 
      towards understanding how these biosynthetic enzymes cooperatively interact to 
      produce the depsipeptide product are expression and isolation of each enzyme to 
      probe its specificity and function. Here we describe the successful production of 
      soluble enzymes from within the ramoplanin locus and the confirmation of their 
      specific role in biosynthesis. These methods may be broadly applicable to the 
      production of biosynthetic enzymes from other natural product biosynthetic gene 
      clusters, especially those that have been refractory to production in 
      heterologous hosts despite standard expression optimization methods.
CI  - Copyright (c) 2011. Published by Elsevier Ltd.
FAU - Hoertz, Amanda J
AU  - Hoertz AJ
AD  - Department of Chemistry, Duke University, Durham, NC 27708, USA.
FAU - Hamburger, James B
AU  - Hamburger JB
FAU - Gooden, David M
AU  - Gooden DM
FAU - Bednar, Maria M
AU  - Bednar MM
FAU - McCafferty, Dewey G
AU  - McCafferty DG
LA  - eng
GR  - R01 AI046611/AI/NIAID NIH HHS/United States
GR  - AI46611/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111207
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Chaperonin 10)
RN  - 0 (Chaperonin 60)
RN  - 0 (Depsipeptides)
RN  - 0 (Glycoproteins)
RN  - EC 6.3.2.- (Peptide Synthases)
RN  - EC 6.3.2.- (non-ribosomal peptide synthase)
RN  - I9BJ0BR28X (ramoplanin A2)
SB  - IM
MH  - Anti-Bacterial Agents/*biosynthesis/pharmacology
MH  - Bacterial Proteins/genetics/metabolism
MH  - Chaperonin 10/genetics/metabolism
MH  - Chaperonin 60/genetics/metabolism
MH  - Depsipeptides/*biosynthesis/pharmacology
MH  - Glycoproteins/*biosynthesis/pharmacology
MH  - Gram-Positive Bacteria/drug effects
MH  - Kinetics
MH  - Micromonosporaceae/genetics
MH  - Multigene Family
MH  - Peptide Synthases/genetics
EDAT- 2012/01/10 06:00
MHDA- 2012/05/12 06:00
CRDT- 2012/01/07 06:00
PHST- 2011/08/04 00:00 [received]
PHST- 2011/11/22 00:00 [revised]
PHST- 2011/11/28 00:00 [accepted]
PHST- 2012/01/07 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/05/12 06:00 [medline]
AID - S0968-0896(11)00998-9 [pii]
AID - 10.1016/j.bmc.2011.11.062 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2012 Jan 15;20(2):859-65. doi: 10.1016/j.bmc.2011.11.062. Epub 
      2011 Dec 7.