CoQ.sub.10 production in Schizosaccharomyces pombe is increased by reduction of glucose levels or deletion of pka1

• Published in: Applied microbiology and biotechnology Vol. 103; no. 12; pp. 4899 - 4915
• Main Authors: Nishida, Ikuhisa, Yokomi, Kazumasa, Hosono, Kouji, Hayashi, Kazuhiro, Matsuo, Yasuhiro, Kaino, Tomohiro, Kawamukai, Makoto
• Format: Journal Article
• Language: English
• Published: Springer 01.06.2019
• Subjects: Biosynthesis; Dextrose; Glucose; Methods; Physiological aspects; Production processes; Protein kinases; Ubiquinones; Yeast fungi
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-019-09843-7

Coenzyme Q (CoQ) is an essential component of the electron transport system that produces ATP in nearly all living cells. CoQ.sub.10 is a popular commercial food supplement around the world, and demand for efficient production of this molecule has increased in recent years. In this study, we explored CoQ.sub.10 production in the fission yeast Schizosaccharomyces pombe. We found that CoQ.sub.10 level was higher in stationary phase than in log phase, and that it increased when the cells were grown in a low concentration of glucose, in maltose, or in glycerol/ethanol medium. Because glucose signaling is mediated by cAMP, we evaluated the involvement of this pathway in CoQ biosynthesis. Loss of Pka1, the catalytic subunit of cAMP-dependent protein kinase, increased production of CoQ.sub.10, whereas loss of the regulatory subunit Cgs1 decreased production. Manipulation of other components of the cAMP-signaling pathway affected CoQ.sub.10 production in a consistent manner. We also found that glycerol metabolism was controlled by the cAMP/PKA pathway. CoQ.sub.10 production by the S. pombe âpka1 reached 0.98 mg/g dry cell weight in medium containing a non-fermentable carbon source [2% glycerol (w/v) and 1% ethanol (w/v) supplemented with 0.5% casamino acids (w/v)], twofold higher than the production in wild-type cells under normal growth conditions. These findings demonstrate that carbon source, growth phase, and the cAMP-signaling pathway are important factors in CoQ.sub.10 production in S. pombe.