TY - JOUR
T1 - Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin
AU - Wang, Kwo Kwang A.
AU - Ng, Tai L.
AU - Wang, Peng
AU - Huang, Zedu
AU - Balskus, Emily P.
AU - van der Donk, Wilfred A.
N1 - Funding Information:
This work was supported by the National Institutes of Health (GM P01 GM077596 to W.A.V. and GM DP2 GM105434 to E.P.B.), a Cottrell Scholar Award (to E.P.B.), a Camille Dreyfus Teacher-Scholar Award (to E.P.B.), and Harvard University (to E.P.B.). We thank Dr. Zhong Li of the Metabolomics Laboratory of the Roy J. Carver Biotechnology Center (UIUC) for acquiring HRMS and MS/MS spectra, and Nicholas Lue (Harvard University) for assisting with chemical synthesis. A subset of NMR spectra was acquired on a 600 MHz instrument purchased with support from NIH Grant S10 RR028833.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Fosfazinomycin and kinamycin are natural products that contain nitrogen–nitrogen (N–N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N–N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N–N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to N–N bond-containing natural products wherein the N–N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N–N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.
AB - Fosfazinomycin and kinamycin are natural products that contain nitrogen–nitrogen (N–N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N–N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N–N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to N–N bond-containing natural products wherein the N–N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N–N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.
UR - http://www.scopus.com/inward/record.url?scp=85053214114&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053214114&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-06083-7
DO - 10.1038/s41467-018-06083-7
M3 - Article
C2 - 30206228
AN - SCOPUS:85053214114
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3687
ER -