Significantly Enhanced Production of Patchoulol in Metabolically Engineered Saccharomyces cerevisiae

• Published in: Journal of agricultural and food chemistry Vol. 67; no. 31; pp. 8590 - 8598
• Main Authors: Ma, Bin, Liu, Min, Li, Zhen-Hai, Tao, Xinyi, Wei, Dong-Zhi, Wang, Feng-Qing
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.08.2019
• Subjects: biosynthesis; cosmetics; enzymes; ergosterol; farnesol; fermentation; genes; glucose; industrialization; metabolic engineering; monosaccharide transport proteins; perfumes; Saccharomyces cerevisiae; sesquiterpenoids; squalene; patchoulol; terpenoids; sesquiterpene; metabolic engineering; Saccharomyces cerevisiae
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.9b03456

Patchoulol, a natural sesquiterpene compound, is widely used in perfumes and cosmetics. Several strategies were adopted to enhance patchoulol production in Saccharomyces cerevisiae: (i) farnesyl pyrophosphate (FPP) synthase and patchoulol synthase were fused to increase the utilization of FPP precursor; (ii) expression of the limiting genes of the mevalonate pathway was enhanced; (iii) squalene synthase was weakened by a glucose-inducible promoter of HXT1 (promoter for hexose transporter) to reduce metabolic flux from FPP to ergosterol; and (iv) farnesol biosynthesis was inhibited to decrease the consumption of FPP. Glucose was used to balance the trade-off between the competitive squalene and patchoulol pathways. The patchoulol production was 59.2 ± 0.7 mg/L in a shaken flask with a final production of 466.8 ± 12.3 mg/L (20.5 ± 0.5 mg/g dry cell weight) combined with fermentation optimization, which was 7.8-fold higher than the reported maximum production. The work significantly promoted the industrialization process of patchoulol production using biobased microbial platforms.