TY - JOUR
T1 - An Uncommon Type II PKS Catalyzes Biosynthesis of Aryl Polyene Pigments
AU - Grammbitter, Gina L.C.
AU - Schmalhofer, Maximilian
AU - Karimi, Kudratullah
AU - Shi, Yi Ming
AU - Schöner, Tim A.
AU - Tobias, Nicholas J.
AU - Morgner, Nina
AU - Groll, Michael
AU - Bode, Helge B.
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/10/23
Y1 - 2019/10/23
N2 - Aryl polyene (APE) pigments are a widely distributed class of bacterial polyketides. So far, little is known about the biosynthesis of these compounds, which are produced by a novel type II polyketide synthase (PKS). We have identified all enzymes involved in APE biosynthesis and determined their peculiar functions. The biosynthesis was reconstituted in vitro, and ACP-bound intermediates were assigned for each reaction step by HPLC-MS. Native mass spectrometry experiments identified four stable complexes: the acyl-carrier proteins ApeE and ApeF bound to the thioesterase ApeK, the dehydratases ApeI and ApeP, and the ketosynthase ApeO in complex with its chain-length factor ApeC. X-ray structures of the heterodimeric ApeO:ApeC and ApeI:ApeP complexes depict striking protein-protein interactions. Altogether, our study elucidated mechanistic aspects of APE biosynthesis that unifies elements of type II fatty acid and PKS systems, but in addition includes novel enzyme complexes.
AB - Aryl polyene (APE) pigments are a widely distributed class of bacterial polyketides. So far, little is known about the biosynthesis of these compounds, which are produced by a novel type II polyketide synthase (PKS). We have identified all enzymes involved in APE biosynthesis and determined their peculiar functions. The biosynthesis was reconstituted in vitro, and ACP-bound intermediates were assigned for each reaction step by HPLC-MS. Native mass spectrometry experiments identified four stable complexes: the acyl-carrier proteins ApeE and ApeF bound to the thioesterase ApeK, the dehydratases ApeI and ApeP, and the ketosynthase ApeO in complex with its chain-length factor ApeC. X-ray structures of the heterodimeric ApeO:ApeC and ApeI:ApeP complexes depict striking protein-protein interactions. Altogether, our study elucidated mechanistic aspects of APE biosynthesis that unifies elements of type II fatty acid and PKS systems, but in addition includes novel enzyme complexes.
UR - http://www.scopus.com/inward/record.url?scp=85064336564&partnerID=8YFLogxK
U2 - 10.1021/jacs.8b10776
DO - 10.1021/jacs.8b10776
M3 - Article
C2 - 30908039
AN - SCOPUS:85064336564
SN - 0002-7863
VL - 141
SP - 16615
EP - 16623
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 42
ER -