Details
| Original language | English |
|---|---|
| Pages (from-to) | 764-769 |
| Number of pages | 6 |
| Journal | CHEMBIOCHEM |
| Volume | 20 |
| Issue number | 6 |
| Early online date | 15 Feb 2019 |
| Publication status | Published - 15 Mar 2019 |
| Externally published | Yes |
Abstract
Armeniaspirols are potent antibiotics containing an unusual spiro[4.4]non-8-ene moiety. Herein, we describe the cloning and functional analysis of the armeniaspirol biosynthetic gene cluster. Gene-inactivation studies and subsequent isolation of previously unknown biosynthetic intermediates shed light on intriguing biosynthetic details. Remarkably, deletion of ams15, which encodes a protein bearing a flavin-binding domain, led to the accumulation of several non-spiro intermediates with various numbers of chlorine substitutions on the pyrrole moiety. The di- and trichloropyrrole species were converted by Streptomyces albus expressing Ams15 into mono- and dichlorinated spiro derivatives, respectively. In addition, in vitro conversion of these non-spiro intermediates into des-N-methyl spiro intermediates by the cell lysate of the same recombinant strain proved Ams15 to be responsible for spiro formation through oxidative dehalogenation.
Keywords
- armeniaspirol, halogenation, oxidative dehalogenation, polyketides, spiro formation
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Chemistry(all)
- Organic Chemistry
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In: CHEMBIOCHEM, Vol. 20, No. 6, 15.03.2019, p. 764-769.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Armeniaspirol Antibiotic Biosynthesis
T2 - Chlorination and Oxidative Dechlorination Steps Affording Spiro[4.4]non-8-ene
AU - Fu, Chengzhang
AU - Xie, Feng
AU - Hoffmann, Judith
AU - Wang, Qiushui
AU - Bauer, Armin
AU - Brönstrup, Mark
AU - Mahmud, Taifo
AU - Müller, Rolf
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Armeniaspirols are potent antibiotics containing an unusual spiro[4.4]non-8-ene moiety. Herein, we describe the cloning and functional analysis of the armeniaspirol biosynthetic gene cluster. Gene-inactivation studies and subsequent isolation of previously unknown biosynthetic intermediates shed light on intriguing biosynthetic details. Remarkably, deletion of ams15, which encodes a protein bearing a flavin-binding domain, led to the accumulation of several non-spiro intermediates with various numbers of chlorine substitutions on the pyrrole moiety. The di- and trichloropyrrole species were converted by Streptomyces albus expressing Ams15 into mono- and dichlorinated spiro derivatives, respectively. In addition, in vitro conversion of these non-spiro intermediates into des-N-methyl spiro intermediates by the cell lysate of the same recombinant strain proved Ams15 to be responsible for spiro formation through oxidative dehalogenation.
AB - Armeniaspirols are potent antibiotics containing an unusual spiro[4.4]non-8-ene moiety. Herein, we describe the cloning and functional analysis of the armeniaspirol biosynthetic gene cluster. Gene-inactivation studies and subsequent isolation of previously unknown biosynthetic intermediates shed light on intriguing biosynthetic details. Remarkably, deletion of ams15, which encodes a protein bearing a flavin-binding domain, led to the accumulation of several non-spiro intermediates with various numbers of chlorine substitutions on the pyrrole moiety. The di- and trichloropyrrole species were converted by Streptomyces albus expressing Ams15 into mono- and dichlorinated spiro derivatives, respectively. In addition, in vitro conversion of these non-spiro intermediates into des-N-methyl spiro intermediates by the cell lysate of the same recombinant strain proved Ams15 to be responsible for spiro formation through oxidative dehalogenation.
KW - armeniaspirol
KW - halogenation
KW - oxidative dehalogenation
KW - polyketides
KW - spiro formation
UR - http://www.scopus.com/inward/record.url?scp=85061603223&partnerID=8YFLogxK
U2 - 10.1002/cbic.201800791
DO - 10.1002/cbic.201800791
M3 - Article
C2 - 30556942
AN - SCOPUS:85061603223
VL - 20
SP - 764
EP - 769
JO - CHEMBIOCHEM
JF - CHEMBIOCHEM
SN - 1439-4227
IS - 6
ER -