Rational Domain Swaps Reveal Insights about Chain Length Control by Ketosynthase Domains in Fungal Nonreducing Polyketide Synthases

A facile genetic methodology in the filamentous fungus Aspergillus nidulans allowed exchange of the starter unit ACP transacylase (SAT) domain in the nonreduced polyketide synthase (NR-PKS) AfoE of the asperfuranone pathway with the SAT domains from 10 other NR-PKSs. The newly created hybrid with the NR-PKS AN3386 is able to accept a longer starter unit in place of the native substrate to create a novel aromatic polyketide in vivo.

[1]  Shu-Lin Chang,et al.  An efficient system for heterologous expression of secondary metabolite genes in Aspergillus nidulans. , 2013, Journal of the American Chemical Society.

[2]  C. Townsend,et al.  Combinatorial domain swaps provide insights into the rules of fungal polyketide synthase programming and the rational synthesis of non-native aromatic products. , 2013, Angewandte Chemie.

[3]  Shu-Lin Chang,et al.  Illuminating the diversity of aromatic polyketide synthases in Aspergillus nidulans. , 2012, Journal of the American Chemical Society.

[4]  N. Kelleher,et al.  Interrogation of global active site occupancy of a fungal iterative polyketide synthase reveals strategies for maintaining biosynthetic fidelity. , 2012, Journal of the American Chemical Society.

[5]  R. Cox,et al.  Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. , 2011, Journal of the American Chemical Society.

[6]  Clay C C Wang,et al.  Engineering of an "unnatural" natural product by swapping polyketide synthase domains in Aspergillus nidulans. , 2011, Journal of the American Chemical Society.

[7]  A. Davidson,et al.  A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans. , 2009, Journal of the American Chemical Society.

[8]  C. Townsend,et al.  Synthetic Strategy of Nonreducing Iterative Polyketide Synthases and the Origin of the Classical “Starter‐Unit Effect” , 2008, Chembiochem : a European journal of chemical biology.

[9]  N. Kelleher,et al.  Deconstruction of Iterative Multidomain Polyketide Synthase Function , 2008, Science.

[10]  Chu-Young Kim,et al.  Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. , 2007, Chemistry & biology.

[11]  Clay C C Wang,et al.  Enzymatic synthesis of aromatic polyketides using PKS4 from Gibberella fujikuroi. , 2007, Journal of the American Chemical Society.

[12]  Yue Ma,et al.  Catalytic Relationships between Type I and Type II Iterative Polyketide Synthases: The Aspergillus parasiticus Norsolorinic Acid Synthase , 2006, Chembiochem : a European journal of chemical biology.

[13]  Chu-Young Kim,et al.  The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase , 2006 .

[14]  S. Osmani,et al.  A Versatile and Efficient Gene-Targeting System for Aspergillus nidulans , 2006, Genetics.

[15]  Chaitan Khosla,et al.  Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway. , 2002, Structure.

[16]  Daniel W. Udwary,et al.  A method for prediction of the locations of linker regions within large multifunctional proteins, and application to a type I polyketide synthase. , 2002, Journal of molecular biology.

[17]  A. Watanabe,et al.  A novel hexaketide naphthalene synthesized by a chimeric polyketide synthase composed of fungal pentaketide and heptaketide synthases , 2002 .

[18]  R. Cox,et al.  First in vitro directed biosynthesis of new compounds by a minimal type II polyketide synthase: evidence for the mechanism of chain length determination. , 2003, Chemical communications.