Deconstruction of Iterative Multidomain Polyketide Synthase Function

@article{citeulike:2725171, abstract = {PksA, which initiates biosynthesis of the environmental carcinogen aflatoxin B1, is one of the multidomain iterative polyketide synthases (IPKSs), a large, poorly understood family of biosynthetic enzymes. We found that dissection of PksA and its reconstitution from selected sets of domains allows the accumulation and characterization of advanced octaketide intermediates bound to the enzyme, permitting the reactions controlled by individual catalytic domains to be identified. A product template (PT) domain unites with the ketosynthase and thioesterase in this IPKS system to assemble precisely seven malonyl-derived building blocks to a hexanoyl starter unit and mediate a specific cyclization cascade. Because the PT domain is common among nonreducing IPKSs, these mechanistic features should prove to be general for IPKS-catalyzed production of aromatic polyketides. 10.1126/science.1154711}, author = {Crawford, Jason M. and Thomas, Paul M. and Scheerer, Jonathan R. and Vagstad, Anna L. and Kelleher, Neil L. and Townsend, Craig A. }, citeulike-article-id = {2725171}, doi = {10.1126/science.1154711}, journal = {Science}, keywords = {fungi, metabolism, pks, polyketide, secondary}, month = {April}, number = {5873}, pages = {243--246}, posted-at = {2008-04-28 00:15:24}, priority = {2}, title = {Deconstruction of Iterative Multidomain Polyketide Synthase Function}, url = {http://dx.doi.org/10.1126/science.1154711}, volume = {320}, year = {2008} }

TY - JOUR ID - citeulike:2725171 L3 - citeulike-article-id:2725171 TI - Deconstruction of Iterative Multidomain Polyketide Synthase Function JF - Science VL - 320 IS - 5873 SP - 243 EP - 246 N2 - PksA, which initiates biosynthesis of the environmental carcinogen aflatoxin B1, is one of the multidomain iterative polyketide synthases (IPKSs), a large, poorly understood family of biosynthetic enzymes. We found that dissection of PksA and its reconstitution from selected sets of domains allows the accumulation and characterization of advanced octaketide intermediates bound to the enzyme, permitting the reactions controlled by individual catalytic domains to be identified. A product template (PT) domain unites with the ketosynthase and thioesterase in this IPKS system to assemble precisely seven malonyl-derived building blocks to a hexanoyl starter unit and mediate a specific cyclization cascade. Because the PT domain is common among nonreducing IPKSs, these mechanistic features should prove to be general for IPKS-catalyzed production of aromatic polyketides. 10.1126/science.1154711 KW - fungi KW - metabolism KW - pks KW - polyketide KW - secondary AU - Crawford, Jason AU - Thomas, Paul AU - Scheerer, Jonathan AU - Vagstad, Anna AU - Kelleher, Neil AU - Townsend, Craig PY - 2008/04/11/ UR - http://dx.doi.org/10.1126/science.1154711 ER -