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|Title:||Genomics-driven discovery of a biosynthetic gene cluster required for the synthesis of BII-Rafflesfungin from the fungus Phoma sp. F3723||Authors:||Sinha, Swati
Leong, Chung Yan
Chen, Swaine L.
Ng, Siew Bee
|Keywords:||DRNTU::Engineering::Computer science and engineering
Biosynthetic Gene Cluster
|Issue Date:||2019||Source:||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||Series/Report no.:||BMC Genomics||Abstract:||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.||URI:||https://hdl.handle.net/10356/105745
|DOI:||10.1186/s12864-019-5762-6||Rights:||© 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.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SCSE Journal Articles|
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