Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis Export

@article{citeulike:695434, abstract = {The pksX gene cluster from Bacillus subtilis is predicted to encode the biosynthesis of an as yet uncharacterized hybrid nonribosomal peptide/polyketide secondary metabolite. We used a combination of biochemical and mass spectrometric techniques to assign functional roles to the proteins AcpK, PksC, PksL, PksF, PksG, PksH, and PksI, and we conclude that they act to incorporate an acetate-derived [beta]-methyl branch on an acetoacetyl-S-carrier protein and ultimately generate a {Delta}2-isoprenyl-S-carrier protein. This work highlights the power of mass spectrometry to elucidate the functions of orphan biosynthetic enzymes, and it details a mechanism by which single-carbon [beta]-branches can be inserted into polyketide-like structures. This pathway represents a noncanonical route to the construction of prenyl units and serves as a prototype for the intersection of isoprenoid and polyketide biosynthetic manifolds in other natural product biosynthetic pathways. 10.1073/pnas.0603148103}, author = {Calderone, Christopher T. and Kowtoniuk, Walter E. and Kelleher, Neil L. and Walsh, Christopher T. and Dorrestein, Pieter C.}, citeulike-article-id = {695434}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0603148103}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/103/24/8977}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16757561}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16757561}, day = {13}, doi = {10.1073/pnas.0603148103}, journal = {PNAS}, keywords = {betabranch, pks}, month = {June}, number = {24}, pages = {8977--8982}, posted-at = {2008-01-21 16:03:41}, priority = {2}, title = {Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis}, url = {http://dx.doi.org/10.1073/pnas.0603148103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:695434 L3 - citeulike-article-id:695434 N2 - The pksX gene cluster from Bacillus subtilis is predicted to encode the biosynthesis of an as yet uncharacterized hybrid nonribosomal peptide/polyketide secondary metabolite. We used a combination of biochemical and mass spectrometric techniques to assign functional roles to the proteins AcpK, PksC, PksL, PksF, PksG, PksH, and PksI, and we conclude that they act to incorporate an acetate-derived [beta]-methyl branch on an acetoacetyl-S-carrier protein and ultimately generate a {Delta}2-isoprenyl-S-carrier protein. This work highlights the power of mass spectrometry to elucidate the functions of orphan biosynthetic enzymes, and it details a mechanism by which single-carbon [beta]-branches can be inserted into polyketide-like structures. This pathway represents a noncanonical route to the construction of prenyl units and serves as a prototype for the intersection of isoprenoid and polyketide biosynthetic manifolds in other natural product biosynthetic pathways. 10.1073/pnas.0603148103 IS - 24 JF - PNAS EP - 8982 TI - Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis VL - 103 SP - 8977 KW - betabranch KW - pks AU - Calderone, Christopher AU - Kowtoniuk, Walter AU - Kelleher, Neil AU - Walsh, Christopher AU - Dorrestein, Pieter PY - 2006/06/13/ UR - http://dx.doi.org/10.1073/pnas.0603148103 ER -