Commodity Chemicals From Engineered Modular Type I Polyketide Synthases.

Satoshi Yuzawa, Amin Zargar, Bo Pang, Leonard Katz, Jay D Keasling

Journal: Methods in enzymology 2019;608():393-415

PMID: 30173771

Full Text on Elsevier Science View on PubMed

Abstract

Reduced polyketides are a subclass of natural products that have a variety of medical, veterinary, and agricultural applications and are well known for their structural diversity. Although these compounds do not resemble each other, they are all made by a class of enzymes known as modular polyketide synthases (PKSs). The commonality of PKS domains/modules that compose PKSs and the understanding of the relationship between the sequence of the PKS and the structure of the compound it produces render modular PKSs as excellent targets for engineering to produce novel compounds with predicted structures. Here, we describe experimental protocols and considerations for modular PKS engineering and two case studies to produce commodity chemicals by engineered PKSs.

Address: Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; Joint BioEnergy Institute, Emeryville, CA, United States.; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; QB3 Institute, University of California, Berkeley, CA, United States.; Joint BioEnergy Institute, Emeryville, CA, United States.; Joint BioEnergy Institute, Emeryville, CA, United States; QB3 Institute, University of California, Berkeley, CA, United States.; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; Joint BioEnergy Institute, Emeryville, CA, United States; QB3 Institute, University of California, Berkeley, CA, United States; Department of Bioengineering, University of California, Berkeley, CA, United States; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, United States; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark; Center for Synthetic Biochemistry, Shenzhen Institutes for Advanced Technologies, Shenzhen, China. Electronic address: [email protected].

DOI: 10.1016/bs.mie.2018.04.027

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MeSH Terms: Actinobacteria, Adipates, Amino Acid Sequence, Catalytic Domain, Computer-Aided Design, Ketones, Metabolic Engineering, Mutagenesis, Polyketide Synthases, Polyketides, Protein Domains, Protein Engineering, Sequence Alignment, Streptomyces, Substrate Specificity