title: Use of pantothenate as a metabolic switch increases the genetic stability of farnesene producing Saccharomyces cerevisiae.
abstract: 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.
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Celeste M
authors: CM
authors: Sandoval
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Marites
authors: M
authors: Ayson
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Nathan
authors: N
authors: Moss
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Bonny
authors: B
authors: Lieu
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Peter
authors: P
authors: Jackson
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Sara P
authors: SP
authors: Gaucher
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Tizita
authors: T
authors: Horning
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Robert H
authors: RH
authors: Dahl
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Judith R
authors: JR
authors: Denery
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA.
authors: Derek A
authors: DA
authors: Abbott
authors: Amyris Inc, 5885 Hollis Street, Ste. 100, Emeryville, CA 94608, USA. Electronic address: meadows@amyris.com.
authors: Adam L
authors: AL
authors: Meadows
mesh_terms: D024861:Genetic Enhancement / Q000379:methods*; D042822:Genomic Instability / Q000235:genetics*; D060847:Metabolic Engineering / Q000379:methods*; D010205:Pantothenic Acid / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D012717:Sesquiterpenes / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D012717:Sesquiterpenes; D010205:Pantothenic Acid
keywords: Farnesene; Genetic stability; Media development; Metabolic switch; Pantothenate; Yeast