Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723
Background: Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis. Results: Therefore, we sequenced th...
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sg-ntu-dr.10356-1057452019-12-06T21:57:07Z Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 Sinha, Swati Nge, Choy-Eng Leong, Chung Yan Ng, Veronica Crasta, Sharon Goh, Falicia Low, Kia-Ngee Zhang, Huibin Arumugam, Prakash Lezhava, Alexander Chen, Swaine L. Kanagasundaram, Yoganathan Ng, Siew Bee Eisenhaber, Frank Eisenhaber, Birgit Mohammad Alfatah School of Computer Science and Engineering DRNTU::Engineering::Computer science and engineering Cyclic Lipodepsipeptide Biosynthetic Gene Cluster Background: Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis. Results: Therefore, we sequenced the genome of one of our Phoma strains (F3723) previously identified as having antifungal activity in a high-throughput screen. We found a biosynthetic gene cluster that was predicted to synthesize a cyclic lipodepsipeptide that differs in the amino acid composition compared to Phomafungin. Antifungal activity guided isolation yielded a new compound, BII-Rafflesfungin, the structure of which was determined. Conclusions: We describe the NRPS-t1PKS cluster ‘BIIRfg’ compatible with the synthesis of the cyclic lipodepsipeptide BII-Rafflesfungin [HMHDA-L-Ala-L-Glu-L-Asn-L-Ser-L-Ser-D-Ser-D-allo-Thr-Gly]. We report new Stachelhaus codes for Ala, Glu, Asn, Ser, Thr, and Gly. We propose a mechanism for BII-Rafflesfungin biosynthesis, which involves the formation of the lipid part by BIIRfg_PKS followed by activation and transfer of the lipid chain by a predicted AMP-ligase on to the first PCP domain of the BIIRfg_NRPS gene. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2019-06-13T08:20:11Z 2019-12-06T21:57:07Z 2019-06-13T08:20:11Z 2019-12-06T21:57:07Z 2019 Journal Article Sinha, S., Nge, C.-E., Leong, C. Y., Ng, V., Crasta, S., Mohammad Alfatah, . . . Eisenhaber, B. (2019). Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723. BMC Genomics, 20(1), 374-. doi: 10.1186/s12864-019-5762-6 https://hdl.handle.net/10356/105745 http://hdl.handle.net/10220/48736 http://dx.doi.org/10.1186/s12864-019-5762-6 en BMC Genomics © 2019 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0. International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 18 p. application/pdf |
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DRNTU::Engineering::Computer science and engineering Cyclic Lipodepsipeptide Biosynthetic Gene Cluster Sinha, Swati Nge, Choy-Eng Leong, Chung Yan Ng, Veronica Crasta, Sharon Goh, Falicia Low, Kia-Ngee Zhang, Huibin Arumugam, Prakash Lezhava, Alexander Chen, Swaine L. Kanagasundaram, Yoganathan Ng, Siew Bee Eisenhaber, Frank Eisenhaber, Birgit Mohammad Alfatah Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
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Background: Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis. Results: Therefore, we sequenced the genome of one of our Phoma strains (F3723) previously identified as having antifungal activity in a high-throughput screen. We found a biosynthetic gene cluster that was predicted to synthesize a cyclic lipodepsipeptide that differs in the amino acid composition compared to Phomafungin. Antifungal activity guided isolation yielded a new compound, BII-Rafflesfungin, the structure of which was determined. Conclusions: We describe the NRPS-t1PKS cluster ‘BIIRfg’ compatible with the synthesis of the cyclic lipodepsipeptide BII-Rafflesfungin [HMHDA-L-Ala-L-Glu-L-Asn-L-Ser-L-Ser-D-Ser-D-allo-Thr-Gly]. We report new Stachelhaus codes for Ala, Glu, Asn, Ser, Thr, and Gly. We propose a mechanism for BII-Rafflesfungin biosynthesis, which involves the formation of the lipid part by BIIRfg_PKS followed by activation and transfer of the lipid chain by a predicted AMP-ligase on to the first PCP domain of the BIIRfg_NRPS gene. |
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School of Computer Science and Engineering |
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School of Computer Science and Engineering Sinha, Swati Nge, Choy-Eng Leong, Chung Yan Ng, Veronica Crasta, Sharon Goh, Falicia Low, Kia-Ngee Zhang, Huibin Arumugam, Prakash Lezhava, Alexander Chen, Swaine L. Kanagasundaram, Yoganathan Ng, Siew Bee Eisenhaber, Frank Eisenhaber, Birgit Mohammad Alfatah |
format |
Article |
author |
Sinha, Swati Nge, Choy-Eng Leong, Chung Yan Ng, Veronica Crasta, Sharon Goh, Falicia Low, Kia-Ngee Zhang, Huibin Arumugam, Prakash Lezhava, Alexander Chen, Swaine L. Kanagasundaram, Yoganathan Ng, Siew Bee Eisenhaber, Frank Eisenhaber, Birgit Mohammad Alfatah |
author_sort |
Sinha, Swati |
title |
Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
title_short |
Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
title_full |
Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
title_fullStr |
Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
title_full_unstemmed |
Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723 |
title_sort |
genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of bii-rafflesfungin from the fungus phoma sp. f3723 |
publishDate |
2019 |
url |
https://hdl.handle.net/10356/105745 http://hdl.handle.net/10220/48736 http://dx.doi.org/10.1186/s12864-019-5762-6 |
_version_ |
1681045861420761088 |