PMID- 29958422
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2079-6382 (Print)
IS  - 2079-6382 (Electronic)
IS  - 2079-6382 (Linking)
VI  - 7
IP  - 3
DP  - 2018 Jun 28
TI  - Lysoquinone-TH1, a New Polyphenolic Tridecaketide Produced by Expressing the 
      Lysolipin Minimal PKS II in Streptomyces albus.
LID - 10.3390/antibiotics7030053 [doi]
LID - 53
AB  - The structural repertoire of bioactive naphthacene quinones is expanded by 
      engineering Streptomyces albus to express the lysolipin minimal polyketide 
      synthase II (PKS II) genes from Streptomyces tendae Tü 4042 (llpD-F) with 
      the corresponding cyclase genes llpCI-CIII. Fermentation of the recombinant 
      strain revealed the two new polyaromatic tridecaketides lysoquinone-TH1 (7, 
      identified) and TH2 (8, postulated structure) as engineered congeners of the 
      dodecaketide lysolipin (1). The chemical structure of 7, a 
      benzo[a]naphthacene-8,13-dione, was elucidated by NMR and HR-MS and confirmed by 
      feeding experiments with [1,2-(13)C(2)]-labeled acetate. Lysoquinone-TH1 (7) is a 
      pentangular polyphenol and one example of such rare extended polyaromatic systems 
      of the benz[a]napthacene quinone type produced by the expression of a minimal PKS 
      II in combination with cyclases in an artificial system. While the natural 
      product lysolipin (1) has antimicrobial activity in nM-range, lysoquinone-TH1 (7) 
      showed only minor potency as inhibitor of Gram-positive microorganisms. The 
      bioactivity profiling of lysoquinone-TH1 (7) revealed inhibitory activity towards 
      phosphodiesterase 4 (PDE4), an important target for the treatment in human health 
      like asthma or chronic obstructive pulmonary disease (COPD). These results 
      underline the availability of pentangular polyphenolic structural skeletons from 
      biosynthetic engineering in the search of new chemical entities in drug 
      discovery.
FAU - Hofeditz, Torben
AU  - Hofeditz T
AD  - Institut fur Organische Chemie, Eberhard Karls Universitat Tubingen, Auf der 
      Morgenstelle 18, 72076 Tubingen, Germany. torben.hofeditz@gmx.de.
FAU - Unsin, Claudia Eva-Maria
AU  - Unsin CE
AD  - Interfakultares Institut fur Mikrobiologie und Infektionsmedizin, Eberhard Karls 
      Universitat Tubingen, Auf der Morgenstelle 28, 72076 Tubingen, Germany. 
      claudia_unsin@yahoo.de.
FAU - Wiese, Jutta
AU  - Wiese J
AD  - GEOMAR, Helmholtz-Zentrum fur Ozeanforschung Kiel, Dusternbrooker Weg 20, 24105 
      Kiel, Germany. jwiese@geomar.de.
FAU - Imhoff, Johannes F
AU  - Imhoff JF
AD  - GEOMAR, Helmholtz-Zentrum fur Ozeanforschung Kiel, Dusternbrooker Weg 20, 24105 
      Kiel, Germany. jimhoff@geomar.de.
FAU - Wohlleben, Wolfgang
AU  - Wohlleben W
AD  - Interfakultares Institut fur Mikrobiologie und Infektionsmedizin, Eberhard Karls 
      Universitat Tubingen, Auf der Morgenstelle 28, 72076 Tubingen, Germany. 
      wolfgang.wohlleben@biotech.uni-tuebingen.de.
AD  - German Center for Infection Research (DZIF), partner site Tubingen, Auf der 
      Morgenstelle 28, 72076 Tubingen, Germany. 
      wolfgang.wohlleben@biotech.uni-tuebingen.de.
FAU - Grond, Stephanie
AU  - Grond S
AD  - Institut fur Organische Chemie, Eberhard Karls Universitat Tubingen, Auf der 
      Morgenstelle 18, 72076 Tubingen, Germany. stephanie.grond@uni-tuebingen.de.
FAU - Weber, Tilmann
AU  - Weber T
AUID- ORCID: 0000-0002-8260-5120
AD  - Interfakultares Institut fur Mikrobiologie und Infektionsmedizin, Eberhard Karls 
      Universitat Tubingen, Auf der Morgenstelle 28, 72076 Tubingen, Germany. 
      tiwe@biosustain.dtu.dk.
AD  - The Novo Nordisk Foundation Center for Biosustainability, Technical University of 
      Denmark, Kemitorvet bygning 220, 2800 Kongens Lyngby, Denmark. 
      tiwe@biosustain.dtu.dk.
LA  - eng
PT  - Journal Article
DEP - 20180628
PL  - Switzerland
TA  - Antibiotics (Basel)
JT  - Antibiotics (Basel, Switzerland)
JID - 101637404
PMC - PMC6164072
OTO - NOTNLM
OT  - aromatic polyketide
OT  - benz[a]naphthacene quinone
OT  - cyclases
OT  - extended polyketide chain
OT  - lysolipin
OT  - minimal PKS II
OT  - pentacyclic angular polyphenol
OT  - tridecaketide
COIS- The authors declare no conflict of interest.
EDAT- 2018/07/01 06:00
MHDA- 2018/07/01 06:01
PMCR- 2018/06/28
CRDT- 2018/07/01 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/06/12 00:00 [revised]
PHST- 2018/06/22 00:00 [accepted]
PHST- 2018/07/01 06:00 [entrez]
PHST- 2018/07/01 06:00 [pubmed]
PHST- 2018/07/01 06:01 [medline]
PHST- 2018/06/28 00:00 [pmc-release]
AID - antibiotics7030053 [pii]
AID - antibiotics-07-00053 [pii]
AID - 10.3390/antibiotics7030053 [doi]
PST - epublish
SO  - Antibiotics (Basel). 2018 Jun 28;7(3):53. doi: 10.3390/antibiotics7030053.