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

被引：47

作者：

Poust, Sean ^{[1
,3
]}

Hagen, Andrew ^{[2
,3
,5
]}

Katz, Leonard ^{[4
,5
]}

Keasling, Jay D. ^{[1
,3
,4
,5
,6
]}

机构：

[1] Univ Calif Berkeley, Dept Biomol & Chem Engn, Berkeley, CA 94270 USA

[2] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94270 USA

[3] Joint BioEnergy Inst, Emeryville, CA 94608 USA

[4] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94270 USA

[5] Synthet Biol Engn Res Ctr, Emeryville, CA 94608 USA

[6] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94270 USA

来源：

CURRENT OPINION IN BIOTECHNOLOGY | 2014年 / 30卷

基金：

美国国家科学基金会;

关键词：

HETEROLOGOUS EXPRESSION; SUBSTRATE-SPECIFICITY; NATURAL-PRODUCTS; RATIONAL DESIGN; SHUTTLE VECTORS; LIBRARIES; DOMAINS; HOST; DOCKING; MODULE;

D O I：

10.1016/j.copbio.2014.04.011

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：32 / 39

页数：8