Peroxisomicine A1 (plant toxin-514) affects normal peroxisome assembly in the yeast Hansenula polymorpha

Previously we demonstrated that peroxisomicine A1 (T-514), a plant toxin is olated from Karwinskia species, has a deteriorating effect on the integrity of peroxisomes of methylotrophic yeasts. Here we describe two strains of H ansenula polymorpha, affected in the normal utilization of methanol as sole source of carbon and energy due to peroxisomicine Al treatment. The two st rains isolated (L17 and RV31) grew poorly on methanol, apparently due to ma lfunctioning of their peroxisomes. Moreover, the cells displayed a high per oxisome turnover rate. We argue that the peroxisomicine Ar induced phenotyp e of both strains is due to a genomic mutation. Strain L17 was functionally complemented after transformation with a H. polymorpha genomic library. Th e complementing 2.8 kb DNA fragment did not contain a well-defined ORF and led us to speculate that it may contain regulatory sequences that. when pre sent in multiple copies in the cell. result in a change of expression of sp ecific genes, thus causing restoration of normal methylotrophic growth. (C) 1999 Elsevier Science Ltd. All rights reserved.