Gardiner Donald M, Jarvis Renée S, Howlett Barbara J
School of Botany, The University of Melbourne, Vic. 3010, Australia.
Fungal Genet Biol. 2005 Mar;42(3):257-63. doi: 10.1016/j.fgb.2004.12.001. Epub 2005 Jan 18.
Epipolythiodioxopiperazine toxins are secreted by a range of fungi, including Leptosphaeria maculans, which produces sirodesmin, and Aspergillus fumigatus, which produces gliotoxin. The L. maculans biosynthetic gene cluster for sirodesmin includes an ABC transporter gene, sirA. Disruption of this gene led to increased secretion of sirodesmin into the medium and an altered ratio of sirodesmin to its immediate precursor. The transcription pattern of a peptide synthetase that catalyses an early step in sirodesmin biosynthesis was elevated in the sirA mutant by 47% over a 7-day period. This was consistent with the finding that the transporter mutant had elevated sirodesmin levels. Despite increased production of sirodesmin, the sirA mutant was more sensitive to both sirodesmin and gliotoxin. The putative gliotoxin transporter gene, gliA, (a major facilitator superfamily transporter) from A. fumigatus complemented the tolerance of the L. maculans sirA mutant to gliotoxin, but not to sirodesmin. The results indicate that SirA contributes to self-protection against sirodesmin in L. maculans and suggest a transporter other than SirA is primarily responsible for efflux of endogenously produced sirodesmin.
表硫代二氧哌嗪毒素由多种真菌分泌,包括产生西罗地辛的大斑壳针孢菌和产生胶毒素的烟曲霉。大斑壳针孢菌中负责西罗地辛生物合成的基因簇包含一个ABC转运蛋白基因sirA。该基因的破坏导致西罗地辛向培养基中的分泌增加,且西罗地辛与其直接前体的比例发生改变。在7天的时间里,sirA突变体中催化西罗地辛生物合成早期步骤的肽合成酶的转录模式提高了47%。这与转运蛋白突变体中西罗地辛水平升高的发现一致。尽管西罗地辛的产量增加,但sirA突变体对西罗地辛和胶毒素都更敏感。来自烟曲霉的假定胶毒素转运蛋白基因gliA(一个主要转运体超家族转运蛋白)补充了大斑壳针孢菌sirA突变体对胶毒素的耐受性,但对西罗地辛无效。结果表明,SirA有助于大斑壳针孢菌对西罗地辛的自我保护,并表明除SirA外的另一种转运蛋白主要负责内源性产生的西罗地辛的外排。