Recent advances in the structural biology of modular polyketide synthases and nonribosomal peptide synthetases |
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| Affiliation: | 1. Department of Chemistry, Stanford University, Stanford, CA 94305, USA;2. Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, 14 2575 Sand Hill Road, MS69, Menlo Park, CA 94025, USA;3. Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA;4. Department of Biochemistry, Stanford University, Stanford, CA 94305, USA;1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan;2. Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan;3. PRESTO, Japan Science and Technology Agency, Saitama, Japan;4. Institute of Natural Medicine, University of Toyama, Toyama, Japan |
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| Abstract: | 
Polyketides and nonribosomal peptides are an important class of natural products with useful bioactivities. These compounds are similarly biosynthesized using enzymes with modular structures despite having different physicochemical properties. These enzymes are attractive targets for bioengineering to produce “unnatural” natural products owing to their modular structures. Therefore, their structures have been studied for a long time; however, the main focus was on truncated-single domains. Surprisingly, there is an increasing number of the structures of whole modules reported, most of which have been enabled through the recent advances in cryogenic electron microscopy technology. In this review, we have summarized the recent advances in the structural elucidation of whole modules. |
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| Keywords: | Polyketide Nonribosomal peptide Modular enzyme X-ray crystallography Cryogenic electron microscopy Structural biology AT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" acyltransferase KR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" ketoreductase KS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" ketosynthase ACP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" acyl carrier protein ER" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" enoyl reductase MT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" methyltransferase C" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" condensation A" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" adenylation PCP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," _" :" peptidyl carrier protein Cy" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" heterocyclization cryo-EM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0145" }," $$" :[{" #name" :" text" ," _" :" cryogenic electron microscopy F" },{" #name" :" keyword" ," $" :{" id" :" kwrd0155" }," $$" :[{" #name" :" text" ," _" :" formyltransferase |
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