Efficient biosynthesis of the plant-derived diterpenoid 14-hydroxy-dehydroabietadiene in Saccharomyces cerevisiae

14-hydroxy-dehydroabietadiene is a precursor in biosynthesis pathway of triptolide in Tripterygium wilfordii and is vital for the production of triptolide and related diterpenes. The 14-hydroxy-dehydroabietadiene was produced in the engineered Saccharomyces cerevisiae WAT11 A-8 through expressing SmMS, TwTPS9, and TwCYP82D274 in combination with BTS1 and ERG20. The expression of TwCPR3 in the S. cerevisiae A-9 and A-10 for providing the electron donating has no obvious role to elevate the production of 14-hydroxy-dehydroabietadiene, but the 14-hydroxy-dehydroabietadiene is 302.73 µg L− 1 after changing S. cerevisiae INVsc1 strain A-13, which is 1.64 times higher than S. cerevisiae initial engineered strain A-8. The fusion of TwCYP82D274 and TwCPR3 in INVsc1 strain A-14, the 14-hydroxy-dehydroabietadiene is 340.26 µg L− 1, which is 1.85 times higher than strain A-8. After enhancing the acetyl-CoA metabolic flux, the 14-hydroxy-dehydroabietadiene is 508.01 µg L− 1 in INVsc1 strain A-15, which is 2.76 times higher than strain A-8. The 14-hydroxy-dehydroabietadiene is 612.76 µg L− 1 in INVsc1 strain A-16, which is 3.33 times higher than strain A-8 when overexpressing the truncated tHMG1. The YPDA medium was provided for engineered strain A-16 fermentation, the 14-hydroxy-dehydroabietadiene is 965.16 µg L− 1 in INVsc1 strain A-16, which is 5.24 times higher than strain A-8 in YPDA medium. These results provide a solid foundation for analyzing the biosynthesis pathway and the industrial-scale production of triptolide and related diterpenes.