Engineering Fungal Nonreducing Polyketide Synthase by Heterologous Expression and Domain Swapping

We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) an...

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Published inOrganic letters Vol. 15; no. 4; pp. 756 - 759
Main Authors Yeh, Hsu-Hua, Chang, Shu-Lin, Chiang, Yi-Ming, Bruno, Kenneth S, Oakley, Berl R, Wu, Tung-Kung, Wang, Clay C. C
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 15.02.2013
Amer Chemical Soc
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Abstract We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbAΔR+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
AbstractList We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbAΔR+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbAΔR+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA In A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbA Delta R+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA in A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbAΔR+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
Heterologous expression of the A. niger NR-PKS gene, e_gw1_19.204 and the adjacent stand-alone R domain gene, est_GWPlus_C_190476 in A. nidulans demonstrated that they belong to a single gene named dtbA. The DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde 1 and 2-ethyl-4,6-dihydroxy-3,5-dimethylbenzaldehyde 2. Generation of DtbA+R-TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
Author Bruno, Kenneth S
Wu, Tung-Kung
Chang, Shu-Lin
Wang, Clay C. C
Oakley, Berl R
Chiang, Yi-Ming
Yeh, Hsu-Hua
AuthorAffiliation Department of Chemistry
Graduate Institute of Pharmaceutical Science
Department of Pharmacology and Pharmaceutical Sciences
Department of Molecular Biosciences
Department of Biotechnology
University of Kansas
Chemical and Biological Process Development Group
University of Southern California
Department of Biological Science and Technology
National Chiao Tung University
Chia Nan University of Pharmacy and Science
Pacific Northwest National Laboratory
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SSID ssj0011529
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Snippet We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA....
Heterologous expression of the A. niger NR-PKS gene, e_gw1_19.204 and the adjacent stand-alone R domain gene, est_GWPlus_C_190476 in A. nidulans demonstrated...
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SubjectTerms aldehydes
Aldehydes - chemistry
Aspergillus nidulans - enzymology
Aspergillus, Polyketide Synthase, Domain Swapping, Thioesterase Domain
BASIC BIOLOGICAL SCIENCES
biosynthesis
carboxylic acids
Carboxylic Acids - chemistry
chemical reactions
chemical structure
Chemistry
Chemistry, Organic
chimerism
engineering
fungi
genes
heterologous gene expression
metabolites
Molecular Structure
Physical Sciences
polyketide synthases
Polyketide Synthases - genetics
Polyketide Synthases - metabolism
polyketides
Protein Engineering - methods
Science & Technology
Title Engineering Fungal Nonreducing Polyketide Synthase by Heterologous Expression and Domain Swapping
URI http://dx.doi.org/10.1021/ol303328t
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=000315254500010
https://www.ncbi.nlm.nih.gov/pubmed/23368695
https://www.proquest.com/docview/1320162987
https://www.proquest.com/docview/2020906348
https://www.osti.gov/biblio/1067959
Volume 15
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