Impact of oxygen supply on production of a novel ganoderic acid in Saccharomyces cerevisiae fermentation

Abstract

A novel bioactive ganoderic acid, 3, 28-dihydroxy-lanosta-8, 24-dien-26-oic-acid (DHLDOA), was recently biosynthesized using a heterologous host Saccharomyces cerevisiae by our group, but its low fermentation titer was an obstacle to large-scale application. In this study, the positive effect of oxygen supply on DHLDOA production by the yeast fermentation in shake-flask was revealed. The highest cell mass with an OD600 value of 27.92 was obtained at initial KLa of 15.6 h−1, and the highest DHLDOA titer of 8.79 mg/L was obtained at initial KLa of 12.6 h−1, which was 1.64- and 1.77-fold that at 4.2 and 15.6 h−1, respectively. Slightly higher pyruvate accumulation, lower citrate level, and adequate precursor pools of DHLDOA anabolism were found to be associated with higher DHLDOA production at initial KLa of 12.6 h−1, in which relatively higher CYP5150L8 and CYP5139G1 activities were also observed. Taken together, the results indicated that oxygen supply caused the global changes of the yeast metabolism, including the DHLDOA biosynthesis. This work will be helpful to further improvement of DHLDOA production by the yeast fermentation.