Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases
| Autor: | Erin E. Drufva, Constance B. Bailey, Elijah G. Hix |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
ER enoylreductase ACP acyl carrier protein Mod module Computer science lcsh:Biotechnology Biomedical Engineering Mutagenesis (molecular biology technique) Computational biology 01 natural sciences Applied Microbiology and Biotechnology Article 03 medical and health sciences Polyketide Synthetic biology EI enoylisomerase MT methyltransferase LM loading module Structural Biology KS ketosynthase lcsh:TP248.13-248.65 010608 biotechnology Polyketide synthase Genetics AT acyltransferase PS pyran synthase Site-directed mutagenesis Saturated mutagenesis lcsh:QH301-705.5 030304 developmental biology Saturation mutagenesis 0303 health sciences biology DEBS 6-deoxyerthronolide B synthase Rational design Protein engineering SNAC N-acetyl cysteamine lcsh:Biology (General) biology.protein PKS polyketide synthase KR ketoreductase DH dehydratase Site directed mutagenesis |
| Zdroj: | Synthetic and Systems Biotechnology, Vol 5, Iss 2, Pp 62-80 (2020) Synthetic and Systems Biotechnology |
| ISSN: | 2405-805X |
| DOI: | 10.1016/j.synbio.2020.04.001 |
| Popis: | Modular polyketide synthases (PKSs) are a multidomain megasynthase class of biosynthetic enzymes that have great promise for the development of new compounds, from new pharmaceuticals to high value commodity and specialty chemicals. Their colinear biosynthetic logic has been viewed as a promising platform for synthetic biology for decades. Due to this colinearity, domain swapping has long been used as a strategy to introduce molecular diversity. However, domain swapping often fails because it perturbs critical protein-protein interactions within the PKS. With our increased level of structural elucidation of PKSs, using judicious targeted mutations of individual residues is a more precise way to introduce molecular diversity with less potential for global disruption of the protein architecture. Here we review examples of targeted point mutagenesis to one or a few residues harbored within the PKS that alter domain specificity or selectivity, affect protein stability and interdomain communication, and promote more complex catalytic reactivity. |
| Databáze: | OpenAIRE |
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