BIOMAT Database Logo BIOMAT Database Logo

Structure of a modular polyketide synthase reducing region. 2023

Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Life Sciences Institute, University of Michigan, Ann Arbor MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.

The chemical scaffolds of numerous therapeutics are polyketide natural products, many formed by bacterial modular polyketide synthases (PKS). The large and flexible dimeric PKS modules have distinct extension and reducing regions. Structures are known for all individual enzyme domains and several extension regions. Here, we report the structure of the full reducing region from a modular PKS, the ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) domains of module 5 of the juvenimicin PKS. The modular PKS-reducing region has a different architecture than the homologous fatty acid synthase (FAS) and iterative PKS systems in its arrangement of domains and dimer interface. The structure reveals a critical role for linker peptides in the domain interfaces, leading to discovery of key differences in KR domains dependent on module composition. Finally, our studies provide insight into the mechanism underlying modular PKS intermediate shuttling by carrier protein (ACP) domains.

UI MeSH Term Description Entries
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D048630 Polyketide Synthases Large enzyme complexes composed of a number of component enzymes that are found in STREPTOMYCES which biosynthesize MACROLIDES and other polyketides. Polyketide Synthase,6-Deoxyerythronolide-B Synthase,Epothilone Polyketide Synthase,Erythromycin Polyketide Synthase,Griseusin Polyketide Synthase,Niddamycin Polyketide Synthase,Polyketide Synthase L1,Polyketide Synthase WA,Rifamycin Polyketide Synthase,Sterigmatocystin Polyketide Synthase,Type I Polyketide Synthase,Type II Polyketide Beta-Ketoacyl Synthase,Urdamycin Polyketide Synthase,WdPKS1 Protein,WhiE Polyketide Synthase,6 Deoxyerythronolide B Synthase,Polyketide Synthase, Epothilone,Polyketide Synthase, Erythromycin,Polyketide Synthase, Griseusin,Polyketide Synthase, Niddamycin,Polyketide Synthase, Rifamycin,Polyketide Synthase, Sterigmatocystin,Polyketide Synthase, Urdamycin,Polyketide Synthase, WhiE,Protein, WdPKS1,Synthase L1, Polyketide,Synthase WA, Polyketide,Synthase, 6-Deoxyerythronolide-B,Synthase, Epothilone Polyketide,Synthase, Erythromycin Polyketide,Synthase, Griseusin Polyketide,Synthase, Niddamycin Polyketide,Synthase, Polyketide,Synthase, Rifamycin Polyketide,Synthase, Sterigmatocystin Polyketide,Synthase, Urdamycin Polyketide,Synthase, WhiE Polyketide,Synthases, Polyketide,Type II Polyketide Beta Ketoacyl Synthase

Related Publications

Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Structure of a modular polyketide synthase.
June 2014, Nature,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Alternative modular polyketide synthase expression controls macrolactone structure.
February 2000, Nature,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Polyketide synthesis in vitro on a modular polyketide synthase.
September 1995, Chemistry & biology,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Heterocomplex structure of a polyketide synthase component involved in modular backbone halogenation.
May 2023, Structure (London, England : 1993),
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Substrate structure-activity relationships guide rational engineering of modular polyketide synthase ketoreductases.
January 2016, Chemical communications (Cambridge, England),
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Programming of erythromycin biosynthesis by a modular polyketide synthase.
September 2010, The Journal of biological chemistry,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
A hybrid modular polyketide synthase obtained by domain swapping.
October 1996, Chemistry & biology,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Modular Oxime Formation by a trans-AT Polyketide Synthase.
August 2023, Angewandte Chemie (International ed. in English),
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Autonomous folding of interdomain regions of a modular polyketide synthase.
May 2007, The FEBS journal,
Tyler M McCullough, and Anya Dhar, and David L Akey, and Jamie R Konwerski, and David H Sherman, and Janet L Smith
Macrodiolide formation by the thioesterase of a modular polyketide synthase.
April 2015, Angewandte Chemie (International ed. in English),
Copied contents to your clipboard!