New and improved tools and methods for enhanced biosynthesis of natural products in microorganisms.
Engineering efficient biosynthesis of natural products in microorganisms requires optimizing gene expression levels to balance metabolite flux distributions and to minimize accumulation of toxic intermediates. Such metabolic optimization is challenged with identifying the right gene targets, and then determining and achieving appropriate gene expression levels. After decades of having a relatively limited set of gene regulation tools available, metabolic engineers are recently enjoying an ever-growing repertoire of more precise and tunable gene expression platforms. Here we review recent applications of natural and designed transcriptional and translational regulatory machinery for engineering biosynthesis of natural products in microorganisms. Customized trans-acting RNAs (sgRNA, asRNA and sRNA), along with appropriate accessory proteins, are allowing for unparalleled tuning of gene expression. Meanwhile metabolite-responsive transcription factors and riboswitches have been implemented in strain screening and evolution, and in dynamic gene regulation. Further refinements and expansions on these platform technologies will circumvent many long-term obstacles in natural products biosynthesis.
Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204, USA.
Zhiqing
Z
Wang
Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204, USA. Electronic address: pccirino@uh.edu.
Patrick C
PC
Cirino
D000818:Animals; D001688:Biological Products / Q000378:metabolism*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods* / Q000639:trends*; D016296:Mutagenesis; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D058615:Synthetic Biology / Q000379:methods / Q000639:trends
D001688:Biological Products; D012329:RNA, Bacterial