Biodegradation-inspired bioproduction of methylacetoin and 2-methyl-2,3-butanediol.
Methylacetoin (3-hydroxy-3-methylbutan-2-one) and 2-methyl-2,3-butanediol are currently obtained exclusively via chemical synthesis. Here, we report, to the best of our knowledge, the first alternative route, using engineered Escherichia coli. The biological synthesis of methylacetoin was first accomplished by reversing its biodegradation, which involved modifying the enzyme complex involved, switching the reaction substrate, and coupling the process to an exothermic reaction. 2-Methyl-2,3-butanediol was then obtained by reducing methylacetoin by exploiting the substrate promiscuity of acetoin reductase. A complete biosynthetic pathway from renewable glucose and acetone was then established and optimized via in vivo enzyme screening and host metabolic engineering, which led to titers of 3.4 and 3.2 g l(-1) for methylacetoin and 2-methyl-2,3-butanediol, respectively. This work presents a biodegradation-inspired approach to creating new biosynthetic pathways for small molecules with no available natural biosynthetic pathway.
Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, China.
Xinglin
X
Jiang
Haibo
H
Zhang
Jianming
J
Yang
Yanning
Y
Zheng
Dexin
D
Feng
Wei
W
Liu
Xin
X
Xu
Yujin
Y
Cao
Huibin
H
Zou
Rubin
R
Zhang
Tao
T
Cheng
Fengjiao
F
Jiao
Mo
M
Xian
D000093:Acetoin / Q000302:isolation & purification / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D001673:Biodegradation, Environmental; D053898:Biosynthetic Pathways / Q000502:physiology*; D002072:Butylene Glycols / Q000302:isolation & purification / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
D002072:Butylene Glycols; D011994:Recombinant Proteins; C053670:2-methyl-2,3-butanediol; D000093:Acetoin; D000429:Alcohol Oxidoreductases; C019801:butanediol dehydrogenase