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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Main Authors: 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
Other Authors: School of Computer Science and Engineering
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/105745
http://hdl.handle.net/10220/48736
http://dx.doi.org/10.1186/s12864-019-5762-6
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spelling 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
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Engineering::Computer science and engineering
Cyclic Lipodepsipeptide
Biosynthetic Gene Cluster
spellingShingle 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
description 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.
author2 School of Computer Science and Engineering
author_facet 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
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