TY - JOUR
T1 - Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis
AU - Lin, Zhenjian
AU - Zachariah, Malcolm M.
AU - Marett, Lenny
AU - Hughen, Ronald W.
AU - Teichert, Russell W.
AU - Concepcion, Gisela P.
AU - Haygood, Margo G.
AU - Olivera, Baldomero M.
AU - Light, Alan R.
AU - Schmidt, Eric W.
PY - 2014/5/23
Y1 - 2014/5/23
N2 - The griseorhodins belong to a family of extensively modified aromatic polyketides that exhibit activities such as inhibition of HIV reverse transcriptase and human telomerase. The vast structural diversity of this group of polyketides is largely introduced by enzymatic oxidations, which can significantly influence the bioactivity profile. Four new compounds, griseorhodins D-F, were isolated from a griseorhodin producer, Streptomyces sp. CN48+, based upon their enhancement of calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, griseorhodins D1 and D2, were shown to be identical to the major, previously uncharacterized products of a grhM mutant in an earlier griseorhodin biosynthesis study. Their structures enabled the establishment of a more complete hypothesis for the biosynthesis of griseorhodins and related compounds. The other two compounds, griseorhodins E and F, represent new products of post-polyketide synthase tailoring in griseorhodin biosynthesis and showed significant binding activity in a human dopamine active transporter assay.
AB - The griseorhodins belong to a family of extensively modified aromatic polyketides that exhibit activities such as inhibition of HIV reverse transcriptase and human telomerase. The vast structural diversity of this group of polyketides is largely introduced by enzymatic oxidations, which can significantly influence the bioactivity profile. Four new compounds, griseorhodins D-F, were isolated from a griseorhodin producer, Streptomyces sp. CN48+, based upon their enhancement of calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, griseorhodins D1 and D2, were shown to be identical to the major, previously uncharacterized products of a grhM mutant in an earlier griseorhodin biosynthesis study. Their structures enabled the establishment of a more complete hypothesis for the biosynthesis of griseorhodins and related compounds. The other two compounds, griseorhodins E and F, represent new products of post-polyketide synthase tailoring in griseorhodin biosynthesis and showed significant binding activity in a human dopamine active transporter assay.
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U2 - 10.1021/np500155d
DO - 10.1021/np500155d
M3 - Article
C2 - 24786728
AN - SCOPUS:84901669299
SN - 0163-3864
VL - 77
SP - 1224
EP - 1230
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 5
ER -