Narrowing the gap between the promise and reality of polyketide synthases as a synthetic biology platform

Journal Article · Mon Dec 01 00:00:00 EST 2014 · CURRENT OPINION IN BIOTECHNOLOGY

DOI:https://doi.org/10.1016/j.copbio.2014.04.011· OSTI ID:1211028

Poust, S; Hagen, A; Katz, L; Keasling, JD

Engineering modular polyketide synthases (PKSs) has the potential to be an effective methodology to produce existing and novel chemicals. However, this potential has only just begun to be realized. We propose the adoption of an iterative design-build-test-learn paradigm to improve PKS engineering. We suggest methods to improve engineered PKS design by learning from laboratory-based selection; adoption of DNA design software and automation to build constructs and libraries more easily; tools for the expression of engineered proteins in a variety of heterologous hosts; and mass spectrometry-based high-throughput screening methods. Finally, lessons learned during iterations of the design-build-test-learn cycle can serve as a knowledge base for the development of a single retrosynthesis algorithm usable by both PKS experts and non-experts alike.

• Sponsoring Organization: USDOE Advanced Research Projects Agency - Energy (ARPA-E)
• DOE Contract Number: DE-0000206-1577
• OSTI ID: 1211028
• Journal Information: CURRENT OPINION IN BIOTECHNOLOGY, Vol. 30; ISSN 0958-1669
• Country of Publication: United States
• Language: English