Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 15451-15461 |
| Seitenumfang | 11 |
| Fachzeitschrift | Journal of Biological Chemistry |
| Jahrgang | 282 |
| Ausgabenummer | 21 |
| Publikationsstatus | Veröffentlicht - 25 Mai 2007 |
| Extern publiziert | Ja |
Abstract
The Pseudomonas fluorescens mupirocin biosynthetic cluster encodes six proteins involved in polyketide biosynthesis and 26 single polypeptides proposed to perform largely tailoring functions. In-frame deletions in the tailoring open reading frames demonstrated that all are required for mupirocin production. A bidirectional promoter region was identified between mupF, which runs counter to other open reading frames and its immediate neighbor macpC, implying the 74-kb cluster consists of two transcriptional units. mupD/E and mupJ/K must be cotranscribed as pairs for normal function implying co-assembly during translation. MupJ and K belong to a widely distributed enzyme pair implicated, with MupH, in methyl addition. Deletion of mupF, a putative ketoreductase, produced a mupirocin analogue with a C-7 ketone. Deletion of mupC, a putative dienoyl CoA reductase, generated an analogue whose structure indicated that MupC is also implicated in control of the oxidation state around the tetrahydropyran ring of monic acid. Double mutants with ΔmupC and ΔmupO, ΔmupU, ΔmupV, or ΔmacpE produced pseudomonic acid B but not pseudomonic acid A, as do the mupO, U, V, and macpE mutants, indicating that MupC must work after MupO, U, and V.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biochemie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularbiologie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Zellbiologie
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in: Journal of Biological Chemistry, Jahrgang 282, Nr. 21, 25.05.2007, S. 15451-15461.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Mutational analysis reveals that all tailoring region genes are required for production of polyketide antibiotic mupirocin by Pseudomonas fluorescens
T2 - Pseudomonic acid B biosynthesis precedes pseudomonic acid A
AU - Hothersall, Joanne
AU - Wu, Ji'en
AU - Rahman, Ayesha S.
AU - Shields, Jennifer A.
AU - Haddock, James
AU - Johnson, Nicola
AU - Cooper, Sian M.
AU - Stephens, Elton R.
AU - Cox, Russell J.
AU - Crosby, John
AU - Willis, Christine L.
AU - Simpson, Thomas J.
AU - Thomas, Christopher M.
PY - 2007/5/25
Y1 - 2007/5/25
N2 - The Pseudomonas fluorescens mupirocin biosynthetic cluster encodes six proteins involved in polyketide biosynthesis and 26 single polypeptides proposed to perform largely tailoring functions. In-frame deletions in the tailoring open reading frames demonstrated that all are required for mupirocin production. A bidirectional promoter region was identified between mupF, which runs counter to other open reading frames and its immediate neighbor macpC, implying the 74-kb cluster consists of two transcriptional units. mupD/E and mupJ/K must be cotranscribed as pairs for normal function implying co-assembly during translation. MupJ and K belong to a widely distributed enzyme pair implicated, with MupH, in methyl addition. Deletion of mupF, a putative ketoreductase, produced a mupirocin analogue with a C-7 ketone. Deletion of mupC, a putative dienoyl CoA reductase, generated an analogue whose structure indicated that MupC is also implicated in control of the oxidation state around the tetrahydropyran ring of monic acid. Double mutants with ΔmupC and ΔmupO, ΔmupU, ΔmupV, or ΔmacpE produced pseudomonic acid B but not pseudomonic acid A, as do the mupO, U, V, and macpE mutants, indicating that MupC must work after MupO, U, and V.
AB - The Pseudomonas fluorescens mupirocin biosynthetic cluster encodes six proteins involved in polyketide biosynthesis and 26 single polypeptides proposed to perform largely tailoring functions. In-frame deletions in the tailoring open reading frames demonstrated that all are required for mupirocin production. A bidirectional promoter region was identified between mupF, which runs counter to other open reading frames and its immediate neighbor macpC, implying the 74-kb cluster consists of two transcriptional units. mupD/E and mupJ/K must be cotranscribed as pairs for normal function implying co-assembly during translation. MupJ and K belong to a widely distributed enzyme pair implicated, with MupH, in methyl addition. Deletion of mupF, a putative ketoreductase, produced a mupirocin analogue with a C-7 ketone. Deletion of mupC, a putative dienoyl CoA reductase, generated an analogue whose structure indicated that MupC is also implicated in control of the oxidation state around the tetrahydropyran ring of monic acid. Double mutants with ΔmupC and ΔmupO, ΔmupU, ΔmupV, or ΔmacpE produced pseudomonic acid B but not pseudomonic acid A, as do the mupO, U, V, and macpE mutants, indicating that MupC must work after MupO, U, and V.
UR - http://www.scopus.com/inward/record.url?scp=34447532448&partnerID=8YFLogxK
U2 - 10.1074/jbc.M701490200
DO - 10.1074/jbc.M701490200
M3 - Article
C2 - 17383964
AN - SCOPUS:34447532448
VL - 282
SP - 15451
EP - 15461
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 21
ER -