Biotechnology and Bioprocess Engineering 2019; 24(3): 413-423  
Technical Advances to Accelerate Modular Type I Polyketide Synthase Engineering towards a Retro-biosynthetic Platform
Bo Pang1,2,†, Luis E. Valencia2,3,†, Jessica Wang, Yao Wan1,2, Ravi Lal, Amin Zargar2, Jay D. Keasling1,2,3,4,5,6,*
1QB3 Institute, University of California, Berkeley, CA 94720, USA
2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
3Department of Bioengineering, University of California, Berkeley, CA 94720, USA
4Department of Chemical & Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA
5Novo Nordisk Foundation Center for Biosustainability, Technical University Denmark, DK2970-Horsholm, Denmark
6Synthetic Biochemistry Center, Institute for Synthetic Biology, Shenzhen Institutes for Advanced Technologies, Shenzhen, Guangdong 518055, China
Correspondence to: Jay D. Keasling
Tel: +510-486-2630
E-mail: jdkeasling@lbl.gov

Equal contribution.
Received: March 6, 2019; Revised: May 6, 2019; Accepted: May 7, 2019; Published online: June 30, 2019.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Modular type I polyketide synthases (PKSs) are multifunctional proteins that are comprised of individual domains organized into modules. These modules act together to assemble complex polyketides from acyl-CoA substrates in a linear fashion. This assembly-line enzymology makes engineered PKSs a potential retro-biosynthetic platform to produce fuels, commodity chemicals, speciality chemicals, and pharmaceuticals in various host microorganisms, including bacteria and fungi. However, the realization of this potential is restricted by practical difficulties in strain engineering, protein overexpression, and titer/yield optimization. These challenges are becoming more possible to overcome due to technical advances in PKS design, engineered heterologous hosts, DNA synthesis and assembly, PKS heterologous expression, and analytical methodology. In this review, we highlight these technical advances in PKS engineering and provide practical considerations thereof.
Keywords: polyketide synthase, retro-biosynthetic analysis, protein engineering, heterologous expression, biofuels, bioproducts


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