Linked Life Data

15984864

Source:http://linkedlifedata.com/resource/pubmed/id/15984864

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2005-6-29
pubmed:abstractText
The study of bioactive natural products has undergone rapid advancement with the cloning and sequencing of large number of gene clusters and the concurrent progress to manipulate complex biosynthetic systems in heterologous hosts. The genetic reconstitution necessitates that the heterologous hosts possess substrate pools that could be coordinately supplied for biosynthesis. Polyketide synthases (PKS) utilize acyl-coenzyme A (CoA) precursors and synthesize polyketides by repetitive decarboxylative condensations. Here we show that acyl-CoA ligases, which belong to a large family of acyl-activating enzymes, possess potential to produce varied starter CoA precursors that could be utilized in polyketide biosynthesis. Incidentally, such protein domains have been recognized in several PKS and nonribosomal peptide synthetase gene clusters. Our studies with mycobacterial fatty acyl-CoA ligases (FACLs) show remarkable tolerance to activate a variety of fatty acids that contain modifications at alpha, beta, omega, and omega-nu positions. This substrate flexibility extends further such that these proteins also efficiently utilize N-acetyl cysteamine, the shorter acceptor terminal portion of CoASH, to produce acyl-SNACs. We show that the in situ generated acyl-CoAs and acyl-SNACs could be channeled to types I and -III PKS systems to produce new metabolites. Together, the promiscuous activity of FACL and PKSs provides new opportunities to expand the repertoire of natural products.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9388-9
pubmed:dateRevised
2008-1-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Promiscuous fatty acyl CoA ligases produce acyl-CoA and acyl-SNAC precursors for polyketide biosynthesis.
pubmed:affiliation
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't