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Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases.
Synth Syst Biotechnol. 2020 Jun; 5(2):62-80.SS

Abstract

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.

Authors+Show Affiliations

Department of Chemistry, University of Tennessee-Knoxville, Knoxville, TN, 37996, USA.Department of Chemistry, University of Tennessee-Knoxville, Knoxville, TN, 37996, USA.Department of Chemistry, University of Tennessee-Knoxville, Knoxville, TN, 37996, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32637664

Citation

Drufva, Erin E., et al. "Site Directed Mutagenesis as a Precision Tool to Enable Synthetic Biology With Engineered Modular Polyketide Synthases." Synthetic and Systems Biotechnology, vol. 5, no. 2, 2020, pp. 62-80.
Drufva EE, Hix EG, Bailey CB. Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases. Synth Syst Biotechnol. 2020;5(2):62-80.
Drufva, E. E., Hix, E. G., & Bailey, C. B. (2020). Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases. Synthetic and Systems Biotechnology, 5(2), 62-80. https://doi.org/10.1016/j.synbio.2020.04.001
Drufva EE, Hix EG, Bailey CB. Site Directed Mutagenesis as a Precision Tool to Enable Synthetic Biology With Engineered Modular Polyketide Synthases. Synth Syst Biotechnol. 2020;5(2):62-80. PubMed PMID: 32637664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Site directed mutagenesis as a precision tool to enable synthetic biology with engineered modular polyketide synthases. AU - Drufva,Erin E, AU - Hix,Elijah G, AU - Bailey,Constance B, Y1 - 2020/05/13/ PY - 2020/02/27/received PY - 2020/04/01/revised PY - 2020/04/06/accepted PY - 2020/7/9/entrez PY - 2020/7/9/pubmed PY - 2020/7/9/medline KW - ACP, acyl carrier protein KW - AT, acyltransferase KW - DEBS, 6-deoxyerthronolide B synthase KW - DH, dehydratase KW - EI, enoylisomerase KW - ER, enoylreductase KW - KR, ketoreductase KW - KS, ketosynthase KW - LM, loading module KW - MT, methyltransferase KW - Mod, module KW - PKS, polyketide synthase KW - PS, pyran synthase KW - Polyketide synthase KW - Protein engineering KW - Rational design KW - SNAC, N-acetyl cysteamine KW - Saturation mutagenesis KW - Site directed mutagenesis KW - Synthetic biology SP - 62 EP - 80 JF - Synthetic and systems biotechnology JO - Synth Syst Biotechnol VL - 5 IS - 2 N2 - 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. SN - 2405-805X UR - https://www.unboundmedicine.com/medline/citation/32637664/Site_directed_mutagenesis_as_a_precision_tool_to_enable_synthetic_biology_with_engineered_modular_polyketide_synthases L2 - https://linkinghub.elsevier.com/retrieve/pii/S2405-805X(20)30020-X DB - PRIME DP - Unbound Medicine ER -
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