PMID- 16416127
OWN - NLM
STAT- MEDLINE
DCOM- 20060703
LR  - 20161124
IS  - 0302-8933 (Print)
IS  - 0302-8933 (Linking)
VI  - 185
IP  - 3
DP  - 2006 Apr
TI  - Effect of glucose limitation and specific mutations in the module 5 enoyl 
      reductase domains in the nystatin and amphotericin polyketide synthases on 
      polyene macrolide biosynthesis.
PG  - 165-71
AB  - Enoyl reductase (ER) domains in module 5 of nystatin and amphotericin polyketide 
      synthase (PKS) are responsible for reduction of the C28-C29 unsaturated bond on 
      the nascent polyketide chain during biosynthesis of both macrolides, resulting in 
      production of tetraenes nystatin A(1) and amphotericin A, respectively. Data 
      obtained in fermentations under glucose limitation conditions demonstrated that 
      the efficiency of the ER5 domain can be influenced by carbon source availability 
      in the amphotericin producer Streptomyces nodosus, but not in the nystatin 
      producer Streptomyces noursei. Two S. noursei ER5 domain mutants were 
      constructed, GG5073SP and S5016N, both producing the heptaene nystatin analogue 
      S44HP with unsaturated C28-C29 bond. While the GG5073SP mutant, with altered ER5 
      NADPH binding site, produced S44HP exclusively, the S5016N mutant synthesized a 
      mixture of nystatin and S44HP. Comparative studies on the S5016N S. noursei 
      mutant and S. nodosus, both producing mixtures of tetraenes and heptaenes, 
      revealed that the ratio between these two types of metabolites was significantly 
      more affected by glucose limitation in S. nodosus. These data suggest that 
      mutation S5016N in NysC "locks" the ER5 domain in a state of intermediate 
      activity which, in contrast to the ER5 domain in the amphotericin PKS, is not 
      significantly influenced by physiological conditions.
FAU - Borgos, Sven E F
AU  - Borgos SE
AD  - Department of Biotechnology, Norwegian University of Science and Technology, 
      NTNU, 7491 Trondheim, Norway.
FAU - Sletta, Havard
AU  - Sletta H
FAU - Fjaervik, Espen
AU  - Fjaervik E
FAU - Brautaset, Trygve
AU  - Brautaset T
FAU - Ellingsen, Trond E
AU  - Ellingsen TE
FAU - Gulliksen, Ole-Martin
AU  - Gulliksen OM
FAU - Zotchev, Sergey B
AU  - Zotchev SB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060114
PL  - Germany
TA  - Arch Microbiol
JT  - Archives of microbiology
JID - 0410427
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Macrolides)
RN  - 0 (Polyenes)
RN  - 1400-61-9 (Nystatin)
RN  - 6KQ75HL677 (amphotericin A)
RN  - 79956-01-7 (Polyketide Synthases)
RN  - 7XU7A7DROE (Amphotericin B)
RN  - EC 1.3.1.9 (Enoyl-(Acyl-Carrier-Protein) Reductase (NADH))
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Amphotericin B/analogs & derivatives/biosynthesis
MH  - Anti-Bacterial Agents/*biosynthesis
MH  - Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/chemistry/*genetics/metabolism
MH  - Glucose/*metabolism
MH  - Macrolides/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Nystatin/biosynthesis
MH  - *Point Mutation
MH  - Polyenes/*metabolism
MH  - Polyketide Synthases/chemistry/genetics/metabolism
MH  - Streptomyces/*enzymology/genetics/growth & development
EDAT- 2006/01/18 09:00
MHDA- 2006/07/04 09:00
CRDT- 2006/01/18 09:00
PHST- 2005/09/15 00:00 [received]
PHST- 2005/12/20 00:00 [accepted]
PHST- 2005/11/30 00:00 [revised]
PHST- 2006/01/18 09:00 [pubmed]
PHST- 2006/07/04 09:00 [medline]
PHST- 2006/01/18 09:00 [entrez]
AID - 10.1007/s00203-005-0083-3 [doi]
PST - ppublish
SO  - Arch Microbiol. 2006 Apr;185(3):165-71. doi: 10.1007/s00203-005-0083-3. Epub 2006 
      Jan 14.