Details
| Original language | English |
|---|---|
| Pages (from-to) | 19231-19242 |
| Number of pages | 12 |
| Journal | Chemistry - A European Journal |
| Volume | 21 |
| Issue number | 52 |
| Publication status | Published - 12 Nov 2015 |
Abstract
Supplementing an AHBA(-) mutant strain of Amycolatopsis mediterranei, the rifamycin producer, with a series of benzoic acid derivatives yielded new tetraketides containing different phenyl groups. These mutasynthetic studies revealed unique reductive properties of A. mediterranei towards nitro- and azidoarenes, leading to the corresponding anilines. In selected cases, the yields of mutaproducts (fermentation products isolated after feeding bacteria with chemically prepared analogs of natural building blocks) obtained are in a range (up to 118 mg L-1) that renders them useful as chiral building blocks for further synthetic endeavors. The configuration of the stereogenic centers at C6 and C7 was determined to be 6R,7S for one representative tetraketide. Importantly, processing beyond the tetraketide stage is not always blocked when the formation of the bicyclic naphthalene precursor cannot occur. This was proven by formation of a bromo undecaketide, an observation that has implications regarding the evolutionary development of rifamycin biosynthesis.
Keywords
- antibiotics, azides, mutasynthesis, natural products, polyketide synthase
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
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In: Chemistry - A European Journal, Vol. 21, No. 52, 12.11.2015, p. 19231-19242.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Evaluation of the Synthetic Potential of an AHBA Knockout Mutant of the Rifamycin Producer Amycolatopsis mediterranei
AU - Bułyszko, Ilona
AU - Dräger, Gerald
AU - Klenge, Anja
AU - Kirschning, Andreas
PY - 2015/11/12
Y1 - 2015/11/12
N2 - Supplementing an AHBA(-) mutant strain of Amycolatopsis mediterranei, the rifamycin producer, with a series of benzoic acid derivatives yielded new tetraketides containing different phenyl groups. These mutasynthetic studies revealed unique reductive properties of A. mediterranei towards nitro- and azidoarenes, leading to the corresponding anilines. In selected cases, the yields of mutaproducts (fermentation products isolated after feeding bacteria with chemically prepared analogs of natural building blocks) obtained are in a range (up to 118 mg L-1) that renders them useful as chiral building blocks for further synthetic endeavors. The configuration of the stereogenic centers at C6 and C7 was determined to be 6R,7S for one representative tetraketide. Importantly, processing beyond the tetraketide stage is not always blocked when the formation of the bicyclic naphthalene precursor cannot occur. This was proven by formation of a bromo undecaketide, an observation that has implications regarding the evolutionary development of rifamycin biosynthesis.
AB - Supplementing an AHBA(-) mutant strain of Amycolatopsis mediterranei, the rifamycin producer, with a series of benzoic acid derivatives yielded new tetraketides containing different phenyl groups. These mutasynthetic studies revealed unique reductive properties of A. mediterranei towards nitro- and azidoarenes, leading to the corresponding anilines. In selected cases, the yields of mutaproducts (fermentation products isolated after feeding bacteria with chemically prepared analogs of natural building blocks) obtained are in a range (up to 118 mg L-1) that renders them useful as chiral building blocks for further synthetic endeavors. The configuration of the stereogenic centers at C6 and C7 was determined to be 6R,7S for one representative tetraketide. Importantly, processing beyond the tetraketide stage is not always blocked when the formation of the bicyclic naphthalene precursor cannot occur. This was proven by formation of a bromo undecaketide, an observation that has implications regarding the evolutionary development of rifamycin biosynthesis.
KW - antibiotics
KW - azides
KW - mutasynthesis
KW - natural products
KW - polyketide synthase
UR - http://www.scopus.com/inward/record.url?scp=84954525898&partnerID=8YFLogxK
U2 - 10.1002/chem.201503548
DO - 10.1002/chem.201503548
M3 - Article
C2 - 25283388
AN - SCOPUS:84954525898
VL - 21
SP - 19231
EP - 19242
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 52
ER -