The concentrations of intracellular co-factors

such as ATP

ADP

NADH and NAD+ vital for energy metabolism within Candida utilis CCTCC M 209298 were measured by HPLC.Based on the levels of co-factors

especially ATP during batch cultivation of C.utilis CCTCC M 209298

we developed a novel culture strategy of L-cysteine addition followed by ATP accumulation(21 h) instead of cell growth ceased(15 h) for further enhanced co-production of S-adenosylmethionine and glutathione using energy metabolic analysis.Subsequently

we combined this strategy with high-cell-density culture of C.utilis CCTCC M 209298

and both high biomass and high co-production of S-adenosylmethionine and glutathione were achieved.The culture strategy under the guidance of ATP concentration was proved to be efficient in terms of full utilization of intracellular residual ATP

together with improvement of co-production of S-adenosylmethionine and glutathione

and the co-production of S-adenosylmethionine and glutathione attained 584.7 mg·L-1 and 1004.4 mg·L-1 from batch and fed-batch fermentation

which were 27.1% and 26.4% higher than the controls

respectively.The results presented in this study provide a feasible strategy for optimization of fermentative processes for enhancing the co-production of analogous useful chemicals biosynthesized by consuming energy.