Δ10(E)-Sphingolipid Desaturase Involved in Fusaruside Mycosynthesis and Stress Adaptation in Fusarium graminearum
Tian, Y; Zhao, GY; Fang, W; Xu, Q; Tan, RX
HERO ID
2902061
Reference Type
Journal Article
Year
2015
Language
English
PMID
| HERO ID | 2902061 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Δ10(E)-Sphingolipid Desaturase Involved in Fusaruside Mycosynthesis and Stress Adaptation in Fusarium graminearum |
| Authors | Tian, Y; Zhao, GY; Fang, W; Xu, Q; Tan, RX |
| Volume | 5 |
| Page Numbers | 10486 |
| Abstract | Sphingolipids are biologically important and structurally distinct cell membrane components. Fusaruside (1) is a 10,11-unsaturated immunosuppressive fungal sphingolipid with medical potentials for treating liver injury and colitis, but its poor natural abundance bottlenecks its druggability. Here, fusaruside is clarified biosynthetically, and its efficacy-related 10,11-double bond can be generated under the regioselective catalysis of an unprecedented Δ10(E)-sphingolipid desaturase (Δ10(E)-SD). Δ10(E)-SD shares 17.7% amino acid sequence similarity with a C9-unmethylated Δ10-sphingolipid desaturase derived from a marine diatom, and 55.7% with Δ8(E)-SD from Fusarium graminearum. Heterologous expression of Δ10(E)-SD in Pichia pastoris has been established to facilitate a reliable generation of 1 through the Δ10(E)-SD catalyzed desaturation of cerebroside B (2), an abundant fungal sphingolipid. Site directed mutageneses show that the conserved histidines of Δ10(E)-SD are essential for the 10,11-desaturation catalysis, which is also preconditioned by the C9-methylation of the substrate. Moreover, Δ10(E)-SD confers improved survival and faster growth to fungal strains at low temperature and high salinity, in parallel with to higher contents of 1 in the mycelia. Collectively, the investigation describes a new Δ10(E)-sphingolipid desaturase with its heterologous expression fundamentalizing a biotechnological supply of 1, and eases the follow-up clarification of the immunosuppression and stress-tolerance mechanism. |
| Doi | 10.1038/srep10486 |
| Pmid | 25994332 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: Scientific reports ISSN: 2045-2322 |
| Is Public | Yes |
| Language Text | English |