Production of geranylgeraniol on overexpression of a prenyl diphosphate synthase fusion gene in Saccharomyces cerevisiae.
An acyclic diterpene alcohol, (E,E,E)-geranylgeraniol (GGOH), is one of the important compounds used as perfume and pharmacological agents. A deficiency of squalene (SQ) synthase activity allows yeasts to accumulate an acyclic sesquiterpene alcohol, (E,E)-farnesol, in their cells. Since sterols are essential for the growth of yeasts, a deficiency of SQ synthase activity makes the addition of supplemental sterols to the culture media necessary. To develop a GGOH production method not requiring any supplemental sterols, we overexpressed HMG1 encoding hydroxymethylglutaryl-CoA reductase and the genes of two prenyl diphosphate synthases, ERG20 and BTS1, in Saccharomyces cerevisiae. A prototrophic diploid coexpressing HMG1 and the ERG20-BTS1 fusion accumulated GGOH with neither disruption of the SQ synthase gene nor the addition of any supplemental sterols. The GGOH content on the diploid cultivation in a 5-l jar fermenter reached 138.8 mg/l under optimal conditions.
Ohto
Chikara
C
Bio Research Lab., Toyota Motor Corporation, 1 Toyota-cho, Toyota 471-8572, Japan.
Muramatsu
Masayoshi
M
Obata
Shusei
S
Sakuradani
Eiji
E
Shimizu
Sakayu
S
D004224:Diterpenes / Q000378:metabolism*; D015870:Gene Expression; D051228:Geranyltranstransferase / Q000235:genetics* / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
D004224:Diterpenes; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C017338:geranylgeraniol; D006903:Hydroxymethylglutaryl CoA Reductases; D051228:Geranyltranstransferase