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The potential that lies in harnessing the chemical synthesis capabilities inherent in living organisms is immense. Here we demonstrate how the biosynthetic machinery of  Lactococcus lactis , can be diverted to make (3 R )-acetoin and the derived 2,3-butanediol isomers  meso -(2,3)-butanediol (m-BDO) and (2 R ,3 R )-butanediol (R-BDO). Efficient production of (3 R )-acetoin was accomplished using a strain where the competing lactate, acetate and ethanol forming pathways had been blocked. By introducing different alcohol dehydrogenases into this strain, either EcBDH from  Enterobacter cloacae  or SadB from  Achromobacter xylosooxidans , it was possible to achieve high-yield production of m-BDO or R-BDO respectively. To achieve biosustainable production of these chemicals from dairy waste, we transformed the above strains with the lactose plasmid pLP712. This enabled efficient production of (3 R )-acetoin, m-BDO and R-BDO from processed whey waste, with titers of 27, 51, and 32 g/L respectively. The corresponding yields obtained were 0.42, 0.47 and 0.40 g/g lactose, which is 82%, 89%, and 76% of maximum theoretical yield respectively. These results clearly demonstrate that  L. lactis  is an excellent choice as a cell factory for transforming lactose containing dairy waste into value added chemicals.

Synthesis of (3R)-acetoin and 2,3-butanediol isomers by metabolically engineered Lactococcus lactis