Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans
In: PLoS genetics, Jg. 9 (2012-10-19), Heft 1
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Zugriff:
Secondary metabolism and development are linked in Aspergillus through the conserved regulatory velvet complex composed of VeA, VelB, and LaeA. The founding member of the velvet complex, VeA, shuttles between the cytoplasm and nucleus in response to alterations in light. Here we describe a new interaction partner of VeA identified through a reverse genetics screen looking for LaeA-like methyltransferases in Aspergillus nidulans. One of the putative LaeA-like methyltransferases identified, LlmF, is a negative regulator of sterigmatocystin production and sexual development. LlmF interacts directly with VeA and the repressive function of LlmF is mediated by influencing the localization of VeA, as over-expression of llmF decreases the nuclear to cytoplasmic ratio of VeA while deletion of llmF results in an increased nuclear accumulation of VeA. We show that the methyltransferase domain of LlmF is required for function; however, LlmF does not directly methylate VeA in vitro. This study identifies a new interaction partner for VeA and highlights the importance of cellular compartmentalization of VeA for regulation of development and secondary metabolism.
Author Summary In recent years there has been increased interest in bioactive small molecules produced by filamentous fungi. Members of the genus Aspergillus are prolific producers of natural products such as penicillin, the cholesterol lowering drug lovastatin, in addition to several toxins, the most famous being aflatoxin. The genetic regulation of fungal natural products is coupled with developmental differentiation through a conserved protein complex termed the velvet complex. The founding member of the complex, velvet (VeA), is a light-regulated protein that shuttles between the cytoplasm and nucleus in response to illumination. Once in the nucleus, VeA interacts with the putative methyltransferase LaeA to positively regulate production of secondary metabolites and with VelB to induce sexual development. We have identified a new interaction partner of VeA that has sequence homology to LaeA. The putative LaeA-like methyltransferase LlmF controls the subcellular localization of VeA in response to light, thereby regulating the downstream outputs of secondary metabolism and development. While the mechanism of the velvet complex remains an enigma, our data suggest that manipulation of protein subcellular localization is an approach that can be used to control production of secondary metabolites.
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Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans
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Autor/in / Beteiligte Person: | Palmer, Jonathan M. ; Keller, Nancy P. ; Calvo, Ana M. ; Theisen, Jeffrey M. ; W. Scott Grayburn ; Duran, Rocio M. |
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Zeitschrift: | PLoS genetics, Jg. 9 (2012-10-19), Heft 1 |
Veröffentlichung: | 2012 |
Medientyp: | unknown |
ISSN: | 1553-7404 (print) |
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