Details
| Original language | English |
|---|---|
| Pages (from-to) | 10113-10117 |
| Number of pages | 5 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 55 |
| Issue number | 34 |
| Publication status | Published - 9 Aug 2016 |
Abstract
Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
Keywords
- cell-line-selective cytotoxin, haprolid, polyketide (bio)synthesis, retrosynthesis, structure elucidation
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- General Chemistry
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In: Angewandte Chemie - International Edition, Vol. 55, No. 34, 09.08.2016, p. 10113-10117.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Isolation, Structure Elucidation, and (Bio)Synthesis of Haprolid, a Cell-Type-Specific Myxobacterial Cytotoxin
AU - Steinmetz, Heinrich
AU - Li, Jun
AU - Fu, Chengzhang
AU - Zaburannyi, Nestor
AU - Kunze, Birgitte
AU - Harmrolfs, Kirsten
AU - Schmitt, Viktoria
AU - Herrmann, Jennifer
AU - Reichenbach, Hans
AU - Höfle, Gerhard
AU - Kalesse, Markus
AU - Müller, Rolf
PY - 2016/8/9
Y1 - 2016/8/9
N2 - Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
AB - Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
KW - cell-line-selective cytotoxin
KW - haprolid
KW - polyketide (bio)synthesis
KW - retrosynthesis
KW - structure elucidation
UR - http://www.scopus.com/inward/record.url?scp=84979255598&partnerID=8YFLogxK
U2 - 10.1002/anie.201603288
DO - 10.1002/anie.201603288
M3 - Article
C2 - 27404448
AN - SCOPUS:84979255598
VL - 55
SP - 10113
EP - 10117
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 34
ER -