The autophagy-related gene Acatg1 is involved in conidiation and cephalosporin production in Acremonium chrysogenum

Autophagy is a highly conserved eukaryotic mechanism for degradation of cellular components and nutrient recycling process. A serine/threonine kinase Atg1 is essential for autophagosome formation under starvation. Acatg1, the homologous gene of atg1 was cloned from the cephalosporin producing fungus Acremonium chrysogenum. Disruption of Acatg1 inhibited the autophagosome formation under starvation and significantly reduced conidia formation. However, exogenous supply of glucose, sucrose, mannitol or inositol restored the conidia formation of the Acatg1 disruption mutant to the wild-type level, suggesting that autophagy is involved in the carbon utilization which is required for cell growth and morphological differentiation. Unexpectedly, the Acatg1 disruption mutant showed strong resistance to exogenous hydrogen peroxide comparing with the wild-type strain. Disruption of Acatg1 also enhanced cephalosporin production at the late stage of fermentation. Consistent with cephalosporin production, the transcription of cephalosporin biosynthetic genes was increased in the Acatg1 disruption mutant and Western blotting demonstrated that the isopenicillin N synthase PcbC involved in cephalosporin biosynthesis was retained at the late stage of fermentation in the Acatg1 disruption mutant while it was sharply reduced in the wild-type strain. These results indicated that Acatg1 plays an important role in both autophagosome formation and cephalosporin production of A. chrysogenum.