Developing tools for engineering hybrid polyketide synthetic pathways.
Bacterial type I polyketide synthases (PKSs) are complex, multifunctional enzymes that synthesize structurally diverse and medicinally important natural products. Given their modular organization, the manipulation of type I PKSs holds tremendous promise for the generation of novel compounds that are not easily accessible by standard synthetic chemical approaches. In theory, hybrid polyketide synthetic pathways can be constructed through the rational recombination of catalytic domains or modules from a variety of PKS systems; however, the general success of this strategy has been elusive, largely due to a poor understanding of the interactions between catalytic domains, as well as PKS modules. Over the past several years, a fundamental knowledge of these issues, and others, has begun to emerge, offering refined strategies for the facile engineering of hybrid polyketide pathways.
Kittendorf
Jeffrey D
JD
University of Michigan Life Sciences Institute, Department of Medicinal Chemistry, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, USA.
Sherman
David H
DH
D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024861:Genetic Enhancement / Q000379:methods*; D018942:Macrolides / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D001426:Bacterial Proteins; D018942:Macrolides; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D048630:Polyketide Synthases