Enhanced accumulation of individual ganoderic acids in a submerged culture of Ganoderma lucidum by the overexpression of squalene synthase gene

• Overexpression of squalene synthase gene (sqs) increased ganoderic acid (GA)’ yields.
• The effect of sqs overexpression on GA production was investigated quantitatively.
• Individual GA (GA-Mk, GA-T, GA-Me, and GA-S) contents were increased by 2.86, 2.67, 1.95, and 1.25-fold, respectively.
• Overexpression of sqs induced the transcription levels of downstream genes.

Ganoderic acids (GAs) produced by Ganoderma lucidum exhibit antitumor and antimetastasis activities. This study aimed to improve the production of individual GAs by engineering the biosynthetic pathway of GAs in G. lucidum through the overexpression of squalene synthase (SQS) gene. SQS catalyzes the first enzymatic step from the mevalonate pathway toward triterpene biosynthesis. The effects of SQS gene overexpression on the accumulation of individual GAs and their intermediates (squalene and lanosterol) by a submerged culture of G. lucidum and on the transcription levels of GA biosynthesis genes in this mushroom were investigated. The maximum contents of GA-Mk, GA-T, GA-Me, and GA-S in G. lucidum overexpressing the SQS gene were 16, 40, 43, and 53 μg/100 mg dry cell weight, respectively, which were 2.86-, 2.67-, 1.95-, and 1.25-fold of those obtained in wild-type strain (WT). The maximum contents of squalene and lanosterol in the SQS gene-overexpression strain were 1.55- and 1.68-fold higher than those of the WT strain. The transcription levels of the biosynthetic genes encoding SQS and lanosterol synthase were up-regulated by 15.6- and 1.93-fold, respectively, in G. lucidum overexpressing the SQS gene, suggesting that increased GA biosynthesis may result from a higher expression of those genes.