SEARCHPKS: a program for detection and analysis of polyketide synthase domains

SEARCHPKS is a software for detection and analysis of polyketide synthase (PKS) domains in a polypeptide sequence. Modular polyketide synthases are unusually large multi-enzymatic multi-domain megasynthases, which are involved in the biosynthesis of pharmaceutically important natural products using an assembly-line mechanism. This program facilitates easy identification of various PKS domains and modules from a given polypeptide sequence. In addition, it also predicts the specificity of the potential acyltransferase domains for various starter and extender precursor units. SEARCHPKS is a user-friendly tool for correlating polyketide chemical structures with the organization of domains and modules in the corresponding modular polyketide synthases. This program also allows the user to extensively analyze and assess the sequence homology of various polyketide synthase domains, thus providing guidelines for carrying out domain and module swapping experiments. SEARCHPKS can also aid in identification of polyketide products made by PKS clusters found in newly sequenced genomes. The computational approach used in SEARCHPKS is based on a comprehensive analysis of various characterized clusters of modular polyketide synthases compiled in PKSDB, a database of modular polyketide synthases. SEARCHPKS can be accessed at http://www.nii.res.in/searchpks.html.

[1]  C. Khosla,et al.  Role of linkers in communication between protein modules. , 2000, Current opinion in chemical biology.

[2]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[3]  J M Ligon,et al.  The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. , 2000, Chemistry & biology.

[4]  D. Hopwood Genetic Contributions to Understanding Polyketide Synthases , 1998 .

[5]  Z Dauter,et al.  The Escherichia coli Malonyl-CoA:Acyl Carrier Protein Transacylase at 1.5-Å Resolution. , 1995, The Journal of Biological Chemistry.

[6]  Gitanjali Yadav,et al.  Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases. , 2003, Journal of molecular biology.

[7]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence data bank and its supplement TrEMBL , 1997, Nucleic Acids Res..

[8]  J. Staunton,et al.  Polyketide biosynthesis: a millennium review. , 2001, Natural product reports.

[9]  Robert D. Finn,et al.  The Pfam protein families database , 2004, Nucleic Acids Res..

[10]  Rajesh S. Gokhale,et al.  Biochemistry of Polyketide Synthases , 2001 .

[11]  S. Donadio,et al.  Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea. , 1992, Gene.

[12]  Benjamin A. Shoemaker,et al.  CDD: a database of conserved domain alignments with links to domain three-dimensional structure , 2002, Nucleic Acids Res..

[13]  L. Katz,et al.  Novel Macrolides Through Genetic Engineering , 2000 .

[14]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[15]  J R Jacobsen,et al.  Tolerance and specificity of polyketide synthases. , 1999, Annual review of biochemistry.