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 in | Organic letters Vol. 15; no. 4; pp. 756 - 759 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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15.02.2013
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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. |
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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 |
AuthorAffiliation_xml | – name: Department of Pharmacology and Pharmaceutical Sciences – name: National Chiao Tung University – name: Chia Nan University of Pharmacy and Science – name: Graduate Institute of Pharmaceutical Science – name: Department of Chemistry – name: Department of Biotechnology – name: Pacific Northwest National Laboratory – name: Department of Molecular Biosciences – name: Department of Biological Science and Technology – name: University of Kansas – name: University of Southern California – name: Chemical and Biological Process Development Group |
Author_xml | – sequence: 1 givenname: Hsu-Hua surname: Yeh fullname: Yeh, Hsu-Hua – sequence: 2 givenname: Shu-Lin surname: Chang fullname: Chang, Shu-Lin – sequence: 3 givenname: Yi-Ming surname: Chiang fullname: Chiang, Yi-Ming – sequence: 4 givenname: Kenneth S surname: Bruno fullname: Bruno, Kenneth S – sequence: 5 givenname: Berl R surname: Oakley fullname: Oakley, Berl R – sequence: 6 givenname: Tung-Kung surname: Wu fullname: Wu, Tung-Kung email: tkwmll@mail.nctu.edu.tw, clayw@usc.edu – sequence: 7 givenname: Clay C. C surname: Wang fullname: Wang, Clay C. C email: tkwmll@mail.nctu.edu.tw, clayw@usc.edu |
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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 |
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