PMID- 10557314
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20231105
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 23
DP  - 1999 Nov 9
TI  - The mycosubtilin synthetase of Bacillus subtilis ATCC6633: a multifunctional 
      hybrid between a peptide synthetase, an amino transferase, and a fatty acid 
      synthase.
PG  - 13294-9
AB  - Bacillus subtilis strain ATCC6633 has been identified as a producer of 
      mycosubtilin, a potent antifungal peptide antibiotic. Mycosubtilin, which belongs 
      to the iturin family of lipopeptide antibiotics, is characterized by a beta-amino 
      fatty acid moiety linked to the circular heptapeptide 
      Asn-Tyr-Asn-Gln-Pro-Ser-Asn, with the second, third, and sixth position present 
      in the D-configuration. The gene cluster from B. subtilis ATCC6633 specifying the 
      biosynthesis of mycosubtilin was identified. The putative operon spans 38 kb and 
      consists of four ORFs, designated fenF, mycA, mycB, and mycC, with strong 
      homologies to the family of peptide synthetases. Biochemical characterization 
      showed that MycB specifically adenylates tyrosine, as expected for mycosubtilin 
      synthetase, and insertional mutagenesis of the operon resulted in a 
      mycosubtilin-negative phenotype. The mycosubtilin synthetase reveals features 
      unique for peptide synthetases as well as for fatty acid synthases: (i) The 
      mycosubtilin synthase subunit A (MycA) combines functional domains derived from 
      peptide synthetases, amino transferases, and fatty acid synthases. MycA 
      represents the first example of a natural hybrid between these enzyme families. 
      (ii) The organization of the synthetase subunits deviates from that commonly 
      found in peptide synthetases. On the basis of the described characteristics of 
      the mycosubtilin synthetase, we present a model for the biosynthesis of iturin 
      lipopeptide antibiotics. Comparison of the sequences flanking the mycosubtilin 
      operon of B. subtilis ATCC6633, with the complete genome sequence of B. subtilis 
      strain 168 indicates that the fengycin and mycosubtilin lipopeptide synthetase 
      operons are exchanged between the two B. subtilis strains.
FAU - Duitman, E H
AU  - Duitman EH
AD  - Department of Genetics, Groningen Biomolecular Sciences and Biotechnology 
      Institute, Kerklaan 30, 9751 NN Haren, The Netherlands.
FAU - Hamoen, L W
AU  - Hamoen LW
FAU - Rembold, M
AU  - Rembold M
FAU - Venema, G
AU  - Venema G
FAU - Seitz, H
AU  - Seitz H
FAU - Saenger, W
AU  - Saenger W
FAU - Bernhard, F
AU  - Bernhard F
FAU - Reinhardt, R
AU  - Reinhardt R
FAU - Schmidt, M
AU  - Schmidt M
FAU - Ullrich, C
AU  - Ullrich C
FAU - Stein, T
AU  - Stein T
FAU - Leenders, F
AU  - Leenders F
FAU - Vater, J
AU  - Vater J
LA  - eng
SI  - GENBANK/AF184956
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - 0 (Lipoproteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (mycosubtilin synthetase)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.6.1.- (Transaminases)
RN  - EC 6.3.2.- (Peptide Synthases)
SB  - IM
MH  - Adenosine Monophosphate/metabolism
MH  - Amino Acid Sequence
MH  - Bacillus subtilis/*enzymology/metabolism
MH  - Base Sequence
MH  - DNA Primers
MH  - Fatty Acid Synthases/chemistry/*metabolism
MH  - Lipoproteins/biosynthesis/chemistry
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/chemistry/genetics/*metabolism
MH  - Multigene Family
MH  - Mutagenesis, Insertional
MH  - Peptide Synthases/chemistry/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Transaminases/chemistry/*metabolism
MH  - Tyrosine/metabolism
PMC - PMC23941
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
PMCR- 2000/05/09
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
PHST- 2000/05/09 00:00 [pmc-release]
AID - 3068 [pii]
AID - 10.1073/pnas.96.23.13294 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13294-9. doi: 
      10.1073/pnas.96.23.13294.