QM/MM study of the taxadiene synthase mechanism

2019 ◽  
Vol 40 (21) ◽  
pp. 1902-1910 ◽  
Author(s):  
Jeaphianne P. M. van Rijn ◽  
Andrés M. Escorcia ◽  
Walter Thiel
Keyword(s):  
2010 ◽  
Vol 9 (12) ◽  
pp. 1734-1740 ◽  
Author(s):  
Khani Sajjad ◽  
Mehdi Sohani Mohammad ◽  
Mahna Nasser ◽  
Barar Jaleh ◽  
Saeed Hejazi Mohammad ◽  
...  

Author(s):  
Behnaz Nowrouzi ◽  
Rachel Li ◽  
Laura E. Walls ◽  
Leopold d’Espaux ◽  
Koray Malci ◽  
...  

AbstractCost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol®), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production. In this study, the key challenge of poor taxadiene synthase (TASY) solubility in S. cerevisiae was revealed, and the strains were strategically engineered to relieve this bottleneck. Multi-copy chromosomal integration of TASY harbouring a selection of fusion solubility tags improved taxadiene titres 22-fold, up to 57 ± 3 mg/L at 30 °C at shake flask scale. The scalability of the process was highlighted through achieving similar titres during scale up to 25 mL and 250 mL in shake flask and bioreactor cultivations, respectively. Maximum taxadiene titres of 129 ± 15 mg/L and 119 mg/L were achieved through shake flask and bioreactor cultivation, respectively, of the optimal strain at a reduced temperature of 20 °C. The results highlight the positive effect of coupling molecular biology tools with bioprocess variable optimisation on synthetic pathway development.HighlightsMaximum taxadiene titre of 129 ± 15 mg/L in Saccharomyces cerevisiae at 20 °CIntegrating fusion protein tagged-taxadiene synthase improved taxadiene titre.Consistent taxadiene titres were achieved at the micro-and mini-bioreactor scales.


2005 ◽  
Vol 127 (21) ◽  
pp. 7834-7842 ◽  
Author(s):  
Yinghua Jin ◽  
David C. Williams ◽  
Rodney Croteau ◽  
Robert M. Coates
Keyword(s):  

BMB Reports ◽  
2012 ◽  
Vol 45 (10) ◽  
pp. 589-594 ◽  
Author(s):  
Mi-Jeong Cha ◽  
Sang-Hee Shim ◽  
Sung-Hong Kim ◽  
Ok-Tae Kim ◽  
Se-Weon Lee ◽  
...  
Keyword(s):  

BMB Reports ◽  
2005 ◽  
Vol 38 (6) ◽  
pp. 668-675 ◽  
Author(s):  
Guoyin Kai ◽  
Lingxia Zhao ◽  
Lei Zhang ◽  
Zhugang Li ◽  
Binhui Guo ◽  
...  

1997 ◽  
Vol 337 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Mehri Hezari ◽  
Raymond E.B. Ketchum ◽  
Donna M. Gibson ◽  
Rodney Croteau

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