DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Polyketide synthases as a platform for chemical product design

 [1];  [2];  [3]; ORCiD logo [4]
  1. Lawrence Berkeley National LaboratoryJoint BioEnergy InstituteEmeryvilleCA94608, Physical Biosciences Div.Lawrence Berkeley National LaboratoryBerkeleyCA94720
  2. Physical Biosciences Div.Lawrence Berkeley National LaboratoryBerkeleyCA94720, Dept. of Energy Agile BioFoundryEmeryvilleCA94608
  3. Lawrence Berkeley National LaboratoryJoint BioEnergy InstituteEmeryvilleCA94608
  4. Lawrence Berkeley National LaboratoryJoint BioEnergy InstituteEmeryvilleCA94608, Physical Biosciences Div.Lawrence Berkeley National LaboratoryBerkeleyCA94720, QB3 Institute, University of California‐BerkeleyEmeryvilleCA94608, Dept. of Chemical and Biomolecular EngineeringUniversity of CaliforniaBerkeleyCA94720, Dept. of BioengineeringUniversity of CaliforniaBerkeleyCA94720
Publication Date:
Sponsoring Org.:
OSTI Identifier:
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
AIChE Journal
Additional Journal Information:
Journal Name: AIChE Journal Journal Volume: 64 Journal Issue: 12; Journal ID: ISSN 0001-1541
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
United States

Citation Formats

Zargar, Amin, Barajas, Jesus F., Lal, Ravi, and Keasling, Jay D. Polyketide synthases as a platform for chemical product design. United States: N. p., 2018. Web. doi:10.1002/aic.16351.
Zargar, Amin, Barajas, Jesus F., Lal, Ravi, & Keasling, Jay D. Polyketide synthases as a platform for chemical product design. United States.
Zargar, Amin, Barajas, Jesus F., Lal, Ravi, and Keasling, Jay D. Mon . "Polyketide synthases as a platform for chemical product design". United States.
title = {Polyketide synthases as a platform for chemical product design},
author = {Zargar, Amin and Barajas, Jesus F. and Lal, Ravi and Keasling, Jay D.},
abstractNote = {},
doi = {10.1002/aic.16351},
journal = {AIChE Journal},
number = 12,
volume = 64,
place = {United States},
year = {2018},
month = {7}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 1 work
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

A Polylinker Approach to Reductive Loop Swaps in Modular Polyketide Synthases
journal, November 2008

  • Kellenberger, Laurenz; Galloway, Ian S.; Sauter, Guido
  • ChemBioChem, Vol. 9, Issue 16
  • DOI: 10.1002/cbic.200800332

Functionally Distinct Modules Operate Two Consecutive α,β→β,γ Double-Bond Shifts in the Rhizoxin Polyketide Assembly Line
journal, December 2009

  • Kusebauch, Björn; Busch, Benjamin; Scherlach, Kirstin
  • Angewandte Chemie International Edition, Vol. 49, Issue 8
  • DOI: 10.1002/anie.200905467

Biosynthesis of 2-Nor-6-deoxyerythronolide B by Rationally Designed Domain Substitution
journal, October 1997

  • Liu, Lu; Thamchaipenet, Arinthip; Fu, Hong
  • Journal of the American Chemical Society, Vol. 119, Issue 43
  • DOI: 10.1021/ja972451y

Terminal Alkene Formation by the Thioesterase of Curacin A Biosynthesis: STRUCTURE OF A DECARBOXYLATING THIOESTERASE
journal, February 2011

  • Gehret, Jennifer J.; Gu, Liangcai; Gerwick, William H.
  • Journal of Biological Chemistry, Vol. 286, Issue 16
  • DOI: 10.1074/jbc.M110.214635

The biorefinery concept: Using biomass instead of oil for producing energy and chemicals
journal, July 2010

Biosynthesis of the Allylmalonyl-CoA Extender Unit for the FK506 Polyketide Synthase Proceeds through a Dedicated Polyketide Synthase and Facilitates the Mutasynthesis of Analogues
journal, February 2011

  • Mo, SangJoon; Kim, Dong Hwan; Lee, Jong Hyun
  • Journal of the American Chemical Society, Vol. 133, Issue 4
  • DOI: 10.1021/ja108399b

Engineering a Polyketide Synthase for In Vitro Production of Adipic Acid
journal, November 2015

Assembly Line Polyketide Synthases: Mechanistic Insights and Unsolved Problems
journal, April 2014

  • Khosla, Chaitan; Herschlag, Daniel; Cane, David E.
  • Biochemistry, Vol. 53, Issue 18
  • DOI: 10.1021/bi500290t

Engineering the acyltransferase substrate specificity of assembly line polyketide synthases
journal, August 2013

  • Dunn, Briana J.; Khosla, Chaitan
  • Journal of The Royal Society Interface, Vol. 10, Issue 85
  • DOI: 10.1098/rsif.2013.0297

Mechanistic Analysis of Acyl Transferase Domain Exchange in Polyketide Synthase Modules
journal, May 2003

  • Hans, Marcus; Hornung, Andreas; Dziarnowski, Agnieszka
  • Journal of the American Chemical Society, Vol. 125, Issue 18
  • DOI: 10.1021/ja029539i

Heterologous Expression and Structural Characterisation of a Pyrazinone Natural Product Assembly Line
journal, October 2012

A Circular Bioeconomy with Biobased Products from CO 2 Sequestration
journal, June 2016

Leveraging microbial biosynthetic pathways for the generation of ‘drop-in’ biofuels
journal, June 2017

Role of natural product diversity in chemical biology
journal, June 2011

Engineered intermodular and intramodular polyketide synthase fusions
journal, September 1997

The structures of type I polyketide synthases
journal, January 2012

  • Keatinge-Clay, Adrian T.
  • Natural Product Reports, Vol. 29, Issue 10
  • DOI: 10.1039/c2np20019h

Polyketide Decarboxylative Chain Termination Preceded by O-Sulfonation in Curacin A Biosynthesis
journal, November 2009

  • Gu, Liangcai; Wang, Bo; Kulkarni, Amol
  • Journal of the American Chemical Society, Vol. 131, Issue 44, p. 16033-16035
  • DOI: 10.1021/ja9071578

Chemical product engineering: An emerging paradigm within chemical engineering
journal, June 2006

  • Costa, R.; Moggridge, G. D.; Saraiva, P. M.
  • AIChE Journal, Vol. 52, Issue 6
  • DOI: 10.1002/aic.10880

Survival of the fittest: An economic perspective on the production of novel biofuels
journal, October 2013

  • Klein-Marcuschamer, Daniel; Blanch, Harvey W.
  • AIChE Journal, Vol. 59, Issue 12
  • DOI: 10.1002/aic.14245

Challenges and opportunities in computer-aided molecular design
journal, October 2015

ClusterMine360: a database of microbial PKS/NRPS biosynthesis
journal, October 2012

  • Conway, Kyle R.; Boddy, Christopher N.
  • Nucleic Acids Research, Vol. 41, Issue D1
  • DOI: 10.1093/nar/gks993

Initiation of Polyene Macrolide Biosynthesis: Interplay between Polyketide Synthase Domains and Modules as Revealed via Domain Swapping, Mutagenesis, and Heterologous Complementation
journal, August 2011

  • Heia, Sondre; Borgos, Sven E. F.; Sletta, Håvard
  • Applied and Environmental Microbiology, Vol. 77, Issue 19
  • DOI: 10.1128/AEM.05781-11

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties
journal, July 2015

  • Krastel, Philipp; Roggo, Silvio; Schirle, Markus
  • Angewandte Chemie International Edition, Vol. 54, Issue 35
  • DOI: 10.1002/anie.201505069

Engineering Broader Specificity into an Antibiotic-Producing Polyketide Synthase
journal, January 1998

Production of doramectin by rational engineering of the avermectin biosynthetic pathway
journal, June 2011

  • Wang, Jian-Bo; Pan, Hai-Xue; Tang, Gong-Li
  • Bioorganic & Medicinal Chemistry Letters, Vol. 21, Issue 11
  • DOI: 10.1016/j.bmcl.2011.04.008

Total Syntheses of (+)-Trienomycins A and F via a Unified Strategy
journal, January 1996

  • Smith, Amos B.; Barbosa, Joseph; Wong, Weichyun
  • Journal of the American Chemical Society, Vol. 118, Issue 35
  • DOI: 10.1021/ja961401a

SBSPKSv2: structure-based sequence analysis of polyketide synthases and non-ribosomal peptide synthetases
journal, April 2017

  • Khater, Shradha; Gupta, Money; Agrawal, Priyesh
  • Nucleic Acids Research, Vol. 45, Issue W1
  • DOI: 10.1093/nar/gkx344

Crystal Structures of Dehydratase Domains from the Curacin Polyketide Biosynthetic Pathway
journal, January 2010

Substrate specificity of the acyl transferase domains of EpoC from the epothilone polyketide synthase
journal, January 2008

  • Petković, Hrvoje; Sandmann, Axel; Challis, Iain R.
  • Org. Biomol. Chem., Vol. 6, Issue 3
  • DOI: 10.1039/B714804F

Gain of Function Mutagenesis of the Erythromycin Polyketide Synthase. 2. Engineered Biosynthesis of an Eight-Membered Ring Tetraketide Lactone
journal, November 1997

  • Kao, Camilla M.; McPherson, Michael; McDaniel, Robert N.
  • Journal of the American Chemical Society, Vol. 119, Issue 46
  • DOI: 10.1021/ja972609e

Olefin Cross-Metathesis in Polymer and Polysaccharide Chemistry: A Review
journal, May 2017

Lessons from natural molecules
journal, December 2004

Computer-aided molecular design: An introduction and review of tools, applications, and solution techniques
journal, December 2016

  • Austin, Nick D.; Sahinidis, Nikolaos V.; Trahan, Daniel W.
  • Chemical Engineering Research and Design, Vol. 116
  • DOI: 10.1016/j.cherd.2016.10.014

Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli
journal, July 2014

Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412
journal, June 2016

  • Tripathi, Ashootosh; Choi, Si-Sun; Sherman, David H.
  • Journal of Industrial Microbiology & Biotechnology, Vol. 43, Issue 8
  • DOI: 10.1007/s10295-016-1790-2

Top value platform chemicals: bio-based production of organic acids
journal, December 2015

Biosynthesis of polyketide synthase extender units
journal, January 2009

  • Chan, Yolande A.; Podevels, Angela M.; Kevany, Brian M.
  • Nat. Prod. Rep., Vol. 26, Issue 1
  • DOI: 10.1039/B801658P

Inversion of Extender Unit Selectivity in the Erythromycin Polyketide Synthase by Acyltransferase Domain Engineering
journal, November 2016

Prediction and Manipulation of the Stereochemistry of Enoylreduction in Modular Polyketide Synthases
journal, November 2008

Beyond ethylmalonyl-CoA: The functional role of crotonyl-CoAcarboxylase/reductase homologs in expanding polyketide diversity
journal, January 2012

  • Wilson, Micheal C.; Moore, Bradley S.
  • Nat. Prod. Rep., Vol. 29, Issue 1
  • DOI: 10.1039/C1NP00082A

Elucidating the mechanism of fluorinated extender unit loading for improved production of fluorine-containing polyketides
journal, January 2017

  • Ad, Omer; Thuronyi, Benjamin W.; Chang, Michelle C. Y.
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 5
  • DOI: 10.1073/pnas.1614196114

Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase
journal, December 2010

  • Kapur, S.; Chen, A. Y.; Cane, D. E.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 51
  • DOI: 10.1073/pnas.1014081107

De novo DNA synthesis using polymerase-nucleotide conjugates
journal, June 2018

  • Palluk, Sebastian; Arlow, Daniel H.; de Rond, Tristan
  • Nature Biotechnology, Vol. 36, Issue 7
  • DOI: 10.1038/nbt.4173

Substrate Flexibility of a Mutated Acyltransferase Domain and Implications for Polyketide Biosynthesis
journal, November 2015

ClusterCAD: a computational platform for type I modular polyketide synthase design
journal, October 2017

  • Eng, Clara H.; Backman, Tyler W. H.; Bailey, Constance B.
  • Nucleic Acids Research, Vol. 46, Issue D1
  • DOI: 10.1093/nar/gkx893

Comprehensive Structural and Biochemical Analysis of the Terminal Myxalamid Reductase Domain for the Engineered Production of Primary Alcohols
journal, August 2015

A functional chimeric modular polyketide synthase generated via domain replacement
journal, October 1996

Role of a Conserved Arginine Residue in Linkers between the Ketosynthase and Acyltransferase Domains of Multimodular Polyketide Synthases
journal, April 2012

  • Yuzawa, Satoshi; Kapur, Shiven; Cane, David E.
  • Biochemistry, Vol. 51, Issue 18
  • DOI: 10.1021/bi300399u

Highly Efficient and Selective Hydrogenation of Aldehydes: A Well-Defined Fe(II) Catalyst Exhibits Noble-Metal Activity
journal, March 2016

PKS and NRPS release mechanisms
journal, January 2010

  • Du, Liangcheng; Lou, Lili
  • Nat. Prod. Rep., Vol. 27, Issue 2
  • DOI: 10.1039/B912037H

Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?
journal, January 2016

  • Horsman, Mark E.; Hari, Taylor P. A.; Boddy, Christopher N.
  • Natural Product Reports, Vol. 33, Issue 2
  • DOI: 10.1039/C4NP00148F

Substrate structure–activity relationships guide rational engineering of modular polyketide synthase ketoreductases
journal, January 2016

  • Bailey, Constance B.; Pasman, Marjolein E.; Keatinge-Clay, Adrian T.
  • Chemical Communications, Vol. 52, Issue 4
  • DOI: 10.1039/C5CC07315D

Comparative Analysis of the Substrate Specificity of trans - versus cis- Acyltransferases of Assembly Line Polyketide Synthases
journal, June 2014

  • Dunn, Briana J.; Watts, Katharine R.; Robbins, Thomas
  • Biochemistry, Vol. 53, Issue 23
  • DOI: 10.1021/bi5004316

Engineered polyketides: Synergy between protein and host level engineering
journal, September 2017

  • Barajas, Jesus F.; Blake-Hedges, Jacquelyn M.; Bailey, Constance B.
  • Synthetic and Systems Biotechnology, Vol. 2, Issue 3
  • DOI: 10.1016/j.synbio.2017.08.005