biostudies-literatureChoi BHNational Research Foundation of Korea650https://www.ebi.ac.uk/biostudies/studies/S-EPMC8950469biostudies-literatureUnknown10(3)Isoprenoids, which are natural compounds with diverse structures, possess several biological activities that are beneficial to humans. A major consideration in isoprenoid production in microbial hosts is that the accumulation of biosynthesized isoprenoid within intracellular membranes may impede balanced cell growth, which may consequently reduce the desired yield of the target isoprenoid. As a strategy to overcome this suggested limitation, we selected peroxisome membranes as depots for the additional storage of biosynthesized isoprenoids to facilitate increased isoprenoid production in <i>Saccharomyces cerevisiae</i>. To maximize the peroxisome membrane storage capacity of <i>S.cerevisiae</i>, the copy number and size of peroxisomes were increased through genetic engineering of the expression of three peroxisome biogenesis-related peroxins (Pex11p, Pex34p, and Atg36p). The genetically enlarged and high copied peroxisomes in <i>S.cerevisiae</i> were stably maintained under a bioreactor fermentation condition. The peroxisome-engineered <i>S.cerevisiae</i> strains were then utilized as host strains for metabolic engineering of heterologous protopanaxadiol pathway. The yields of protopanaxadiol from the engineered peroxisome strains were ca 78% higher than those of the parent strain, which strongly supports the rationale for harnessing the storage capacity of the peroxisome membrane to accommodate the biosynthesized compounds. Consequently, this study presents in-depth knowledge on peroxisome biogenesis engineering in <i>S.cerevisiae</i> and could serve as basic information for improvement in ginsenosides production and as a potential platform to be utilized for other isoprenoids.MicroorganismsOrganelle Engineering in Yeast: Enhanced Production of Protopanaxadiol through Manipulation of Peroxisome Proliferation in <i>Saccharomyces cerevisiae</i>.PMC89504692020R1A2C30088892019R1A6A110514712020M3A9I5037889Choi BHKim SCKang HJLee PCfalseOrganelle Engineering in Yeast: Enhanced Production of Protopanaxadiol through Manipulation of Peroxisome Proliferation in <i>Saccharomyces cerevisiae</i>.Isoprenoids, which are natural compounds with diverse structures, possess several biological activities that are beneficial to humans. A major consideration in isoprenoid production in microbial hosts is that the accumulation of biosynthesized isoprenoid within intracellular membranes may impede balanced cell growth, which may consequently reduce the desired yield of the target isoprenoid. As a strategy to overcome this suggested limitation, we selected peroxisome membranes as depots for the additional storage of biosynthesized isoprenoids to facilitate increased isoprenoid production in <i>Saccharomyces cerevisiae</i>. To maximize the peroxisome membrane storage capacity of <i>S.cerevisiae</i>, the copy number and size of peroxisomes were increased through genetic engineering of the expression of three peroxisome biogenesis-related peroxins (Pex11p, Pex34p, and Atg36p). The genetically enlarged and high copied peroxisomes in <i>S.cerevisiae</i> were stably maintained under a bioreactor fermentation condition. The peroxisome-engineered <i>S.cerevisiae</i> strains were then utilized as host strains for metabolic engineering of heterologous protopanaxadiol pathway. The yields of protopanaxadiol from the engineered peroxisome strains were ca 78% higher than those of the parent strain, which strongly supports the rationale for harnessing the storage capacity of the peroxisome membrane to accommodate the biosynthesized compounds. Consequently, this study presents in-depth knowledge on peroxisome biogenesis engineering in <i>S.cerevisiae</i> and could serve as basic information for improvement in ginsenosides production and as a potential platform to be utilized for other isoprenoids.2022-01-01T00:00:00Z2022 Mar2026-04-08T17:49:53.755Z2025-04-21T17:09:17.525ZS-EPMC89504693533622510.3390/microorganisms10030650