초록
<P><B>Significance</B></P><P>This work establishes a semicontinuous process for efficient and complete upgrading of low-strength acetic acid into lipids. By implementing control strategies in response to the time-varying nature of cell metabolism, we achieved and sustained lipid yields close to the theoretical maximum while maintaining high productivities. The control algorithm was designed to respond to readily available real-time measurements and basic principles, which is ideal for industrial applications. Overall, our process scheme can directly take in dilute nutrient streams that are difficult and costly to purify and is able to biologically convert them into highly concentrated value-added products. This design significantly reduces the energy costs associated with processes using dilute feedstocks, which typically require initial concentration of the feed.</P><P>Acetic acid can be generated through syngas fermentation, lignocellulosic biomass degradation, and organic waste anaerobic digestion. Microbial conversion of acetate into triacylglycerols for biofuel production has many advantages, including low-cost or even negative-cost feedstock and environmental benefits. The main issue stems from the dilute nature of acetate produced in such systems, which is costly to be processed on an industrial scale. To tackle this problem, we established an efficient bioprocess for converting dilute acetate into lipids, using the oleaginous yeast <I>Yarrowia lipolytica</I> in a semicontinuous system. The implemented design used low-strength acetic acid in both salt and acid forms as carbon substrate and a cross-filtration module for cell recycling. Feed controls for acetic acid and nitrogen based on metabolic models and online measurement of the respiratory quotient were used. The optimized process was able to sustain high-density cell culture using acetic acid of only 3% and achieved a lipid titer, yield, and productivity of 115 g/L, 0.16 g/g, and 0.8 g⋅L<SUP>−1</SUP>⋅h<SUP>−1</SUP>, respectively. No carbon substrate was detected in the effluent stream, indicating complete utilization of acetate. These results represent a more than twofold increase in lipid production metrics compared with the current best-performing results using concentrated acetic acid as carbon feed.</P>