酿酒酵母
生物反应器
代谢工程
酵母
生物化学
产量(工程)
生物量(生态学)
生物
拉伤
焊剂(冶金)
化学
突变体
酶
基因
植物
有机化学
解剖
冶金
材料科学
农学
作者
Celeste M. Sandoval,Marites Ayson,Nathan A. Moss,Bonny Lieu,Peter Jackson,Sara P. Gaucher,Tizita Horning,Robert H. Dahl,Judith R. Denery,Derek A. Abbott,Adam L. Meadows
标识
DOI:10.1016/j.ymben.2014.07.006
摘要
We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A, from the growth medium of Saccharomyces cerevisiae engineered to produce β-farnesene reduced the strain׳s farnesene flux by 70%, but increased its viability, growth rate and biomass yield. Conversely, the growth rate and biomass yield of wild-type yeast were reduced. Cultivation in media lacking pantothenate eliminates the growth advantage of low-producing mutants, leading to improved production upon scale-up to lab-scale bioreactor testing. An omics investigation revealed that when exogenous pantothenate levels are limited, acyl-CoA metabolites decrease, β-oxidation decreases from unexpectedly high levels in the farnesene producer, and sterol and fatty acid synthesis likely limits the growth rate of the wild-type strain. Thus pantothenate supplementation can be utilized as a “metabolic switch” for tuning the synthesis rates of molecules relying on CoA intermediates and aid the economic scale-up of strains producing acyl-CoA derived molecules to manufacturing facilities.
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