Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis

Zhenjian Lin, Malcolm M. Zachariah, Lenny Marett, Ronald W. Hughen, Russell W. Teichert, Gisela P. Concepcion, Margo Haygood, Baldomero M. Olivera, Alan R. Light, Eric W. Schmidt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1224-1230
Number of pages7
JournalJournal of Natural Products
Volume77
Issue number5
DOIs
StatePublished - May 23 2014

Fingerprint

Biosynthesis
Polyketides
Assays
Polyketide Synthases
HIV Reverse Transcriptase
Dopamine Plasma Membrane Transport Proteins
Primary Cell Culture
Telomerase
Spinal Ganglia
Streptomyces
Bioactivity
Cell culture
griseorhodins
griseorhodin D
griseorhodin F
Dopamine
Calcium
Oxidation

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Lin, Z., Zachariah, M. M., Marett, L., Hughen, R. W., Teichert, R. W., Concepcion, G. P., ... Schmidt, E. W. (2014). Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis. Journal of Natural Products, 77(5), 1224-1230. https://doi.org/10.1021/np500155d

Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis. / Lin, Zhenjian; Zachariah, Malcolm M.; Marett, Lenny; Hughen, Ronald W.; Teichert, Russell W.; Concepcion, Gisela P.; Haygood, Margo; Olivera, Baldomero M.; Light, Alan R.; Schmidt, Eric W.

In: Journal of Natural Products, Vol. 77, No. 5, 23.05.2014, p. 1224-1230.

Research output: Contribution to journalArticle

Lin, Z, Zachariah, MM, Marett, L, Hughen, RW, Teichert, RW, Concepcion, GP, Haygood, M, Olivera, BM, Light, AR & Schmidt, EW 2014, 'Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis', Journal of Natural Products, vol. 77, no. 5, pp. 1224-1230. https://doi.org/10.1021/np500155d
Lin, Zhenjian ; Zachariah, Malcolm M. ; Marett, Lenny ; Hughen, Ronald W. ; Teichert, Russell W. ; Concepcion, Gisela P. ; Haygood, Margo ; Olivera, Baldomero M. ; Light, Alan R. ; Schmidt, Eric W. / Griseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in griseorhodin biosynthesis. In: Journal of Natural Products. 2014 ; Vol. 77, No. 5. pp. 1224-1230.
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