eprintid: 18844
rev_number: 16
userid: 1419
dir: disk0/00/01/88/44
datestamp: 2013-06-07 20:04:04
lastmod: 2019-02-02 16:56:29
status_changed: 2013-06-07 20:04:04
type: article
metadata_visibility: show
item_issues_count: 0
eprint_status: archive
creators_name: Gu, L
creators_name: Wang, B
creators_name: Kulkarni, A
creators_name: Gehret, JJ
creators_name: Lloyd, KR
creators_name: Gerwick, L
creators_name: Gerwick, WH
creators_name: Wipf, P
creators_name: Håkansson, K
creators_name: Smith, JL
creators_name: Sherman, DH
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creators_email: pwipf@pitt.edu
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title: Polyketide decarboxylative chain termination preceded by O-sulfonation in curacin A biosynthesis
ispublished: pub
divisions: sch_as_chemistry
full_text_status: public
abstract: (Figure Presented) Biosynthetic innovation in natural product systems is driven by the recruitment of new genes and enzymes into these complex pathways. Here, an unprecedented decarboxylative chain termination mechanism is described for the polyketide synthase of curacin A, an anticancer lead compound isolated from the marine cyanobacterium Lyngbya majuscula. The unusual chain termination module containing adjacent sulfotransferase (ST) and thioesterase (TE) catalytic domains embedded in CurM was biochemically characterized. The TE was proved to catalyze a hydrolytic chain release of the polyketide chain elongation intermediate. Moreover, a selective ST-mediated sulfonation of the (R)-β-hydroxyl group was found to precede TE-mediated hydrolysis, triggering a successive decarboxylative elimination and resulting in the formation of a rare terminal olefin in the final metabolite. Copyright © 2009 American Chemical Society.
date: 2009-11-27
date_type: published
publication: Journal of the American Chemical Society
volume: 131
number: 44
pagerange: 16033 - 16035
refereed: TRUE
issn: 0002-7863
id_number: 10.1021/ja9071578
other_id: NLM NIHMS183561
other_id: NLM PMC2839324
pmcid: PMC2839324
pmid: 19835378
mesh_headings: Antineoplastic Agents
mesh_headings: Bacterial Proteins
mesh_headings: Cyanobacteria
mesh_headings: Cyclopropanes--metabolism
mesh_headings: Decarboxylation
mesh_headings: Macrolides--metabolism
mesh_headings: Metabolic Networks and Pathways
mesh_headings: Polyketide Synthases--metabolism
mesh_headings: Sulfones
mesh_headings: Sulfotransferases
mesh_headings: Thiazoles--metabolism
mesh_headings: Tubulin Modulators
chemical_names: Antineoplastic Agents
chemical_names: Bacterial Proteins
chemical_names: Cyclopropanes
chemical_names: Macrolides
chemical_names: Sulfones
chemical_names: Thiazoles
chemical_names: Tubulin Modulators
chemical_names: curacin A
chemical_names: Polyketide Synthases
chemical_names: Sulfotransferases
citation:   Gu, L and Wang, B and Kulkarni, A and Gehret, JJ and Lloyd, KR and Gerwick, L and Gerwick, WH and Wipf, P and Håkansson, K and Smith, JL and Sherman, DH  (2009) Polyketide decarboxylative chain termination preceded by O-sulfonation in curacin A biosynthesis.  Journal of the American Chemical Society, 131 (44).  16033 - 16035.  ISSN 0002-7863     
document_url: http://d-scholarship-dev.library.pitt.edu/18844/1/licence.txt