2017
DOI: 10.1128/aem.00892-17
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Laboratory Evolution of a Biotin-Requiring Saccharomyces cerevisiae Strain for Full Biotin Prototrophy and Identification of Causal Mutations

Abstract: Biotin prototrophy is a rare, incompletely understood, and industrially relevant characteristic of Saccharomyces cerevisiae strains. The genome of the haploid laboratory strain CEN.PK113-7D contains a full complement of biotin biosynthesis genes, but its growth in biotin-free synthetic medium is extremely slow (specific growth rate [] Ϸ 0.01 h Ϫ1 ). Four independent evolution experiments in repeated batch cultures and accelerostats yielded strains whose growth rates ( Յ 0.36 h Ϫ1 ) in biotin-free and biotin-su… Show more

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Cited by 32 publications
(28 citation statements)
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“…Gaining understanding of the biochemistry and genetics of vitamin metabolism is of high relevance for optimization of vitamin de novo synthesis. Design of prototrophic strains can be informed by genetic and physiological analysis of fully prototrophic strains and species as well as by evolutionary engineering of strains for fast growth in the absence of growth factors (Bracher et al, ; Mans, Daran, & Pronk, ). Knowledge derived from such studies may, ultimately, enable the construction of yeast cell factories for vitamin production.…”
Section: Discussionmentioning
confidence: 99%
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“…Gaining understanding of the biochemistry and genetics of vitamin metabolism is of high relevance for optimization of vitamin de novo synthesis. Design of prototrophic strains can be informed by genetic and physiological analysis of fully prototrophic strains and species as well as by evolutionary engineering of strains for fast growth in the absence of growth factors (Bracher et al, ; Mans, Daran, & Pronk, ). Knowledge derived from such studies may, ultimately, enable the construction of yeast cell factories for vitamin production.…”
Section: Discussionmentioning
confidence: 99%
“…Overexpression of BIO1 , but not BIO6 , from a multicopy plasmid sufficed to increase specific growth rates of the nonevolved strain on biotin‐free CDMY without biotin from 0.01 to 0.15 hr −1 . Despite its unknown function, these results show that BIO1 is a key bottleneck of de novo biotin synthesis in S. cerevisiae (Bracher et al, ). Strategies to generate biotin‐prototrophic S. cerevisiae strains are likely to benefit from elucidation of the reaction catalyzed by Bio1.…”
Section: Vitamins That Act As Enzyme Cofactorsmentioning
confidence: 92%
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“…Besides the added sequence, 6 Kbp of sequence of the short-read assembly was not present in the nanopore assembly, mostly consisting of small unplaced contigs. Notably the absence of BIO1 and BIO6 in the assembly was unexpected, as it constituted a marked difference between CEN.PK113-7D and many other strains that enables biotin prototrophy (Bracher et al 2017). Both genes were present in the nanopore reads, but were unassembled likely due to the lack of reads long enough to resolve this subtelomeric region (a fragment of BIO1 is located at the right end of chromosome I).…”
Section: Discussionmentioning
confidence: 99%