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| - | [[Image:1jwx.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1jwx| PDB=1jwx | SCENE= }} | | {{STRUCTURE_1jwx| PDB=1jwx | SCENE= }} |
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| - | '''Chalcone Synthase--F215S mutant'''
| + | ===Chalcone Synthase--F215S mutant=== |
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| - | ==Overview==
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| - | Type III polyketide synthases (PKS) generate an array of natural products by condensing multiple acetyl units derived from malonyl-CoA to thioester-linked starter molecules covalently bound in the PKS active site. One strategy adopted by Nature for increasing the functional diversity of these biosynthetic enzymes involves modifying polyketide assembly by altering the preference for starter molecules. Chalcone synthase (CHS) is a ubiquitous plant PKS and the first type III PKS described functionally and structurally. Guided by the three-dimensional structure of CHS, Phe-215 and Phe-265, which are situated at the active site entrance, were targeted for site-directed mutagenesis to diversify CHS activity. The resulting mutants were screened against a panel of aliphatic and aromatic CoA-linked starter molecules to evaluate the degree of starter molecule specificity in CHS. Although wild-type CHS accepts a number of natural CoA thioesters, it does not use N-methylanthraniloyl-CoA as a substrate. Substitution of Phe-215 by serine yields a CHS mutant that preferentially accepts this CoA-thioester substrate to generate a novel alkaloid, namely N-methylanthraniloyltriacetic acid lactone. These results demonstrate that a point mutation in CHS dramatically shifts the molecular selectivity of this enzyme. This structure-based approach to metabolic redesign represents an initial step toward tailoring the biosynthetic activity of plant type III PKS.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11959984}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11959984 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11959984}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Ketoacyl synthase]] | | [[Category: Ketoacyl synthase]] |
| | [[Category: Polyketide synthase]] | | [[Category: Polyketide synthase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:01:41 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:40:54 2008'' |
Revision as of 16:40, 28 July 2008
Template:STRUCTURE 1jwx
Chalcone Synthase--F215S mutant
Template:ABSTRACT PUBMED 11959984
About this Structure
1JWX is a Single protein structure of sequence from Medicago sativa. Full crystallographic information is available from OCA.
Reference
Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity., Jez JM, Bowman ME, Noel JP, Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5319-24. PMID:11959984
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