BioChem - DOS

Comparative genomics and transcriptomics analysis-guided metabolic engineering of Propionibacterium acidipropionici for improved propionic acid production

Biotechnology and bioengineering

Guan, Ningzi; Du, Bin; Li, Jianghua; Shin, Hyun‐ dong; Chen, Rachel R.; Du, Guocheng; Chen, Jian; Liu, Long

<P><B>Abstract</B></P><P>Acid stress induced by the accumulation of organic acids during the fermentation of propionibacteria is a severe limitation in the microbial production of propionic acid (PA). To enhance the acid resistance of strains, the tolerance mechanisms of cells must first be understood. In this study, comparative genomic and transcriptomic analyses were conducted on wild&#8208;type and acid&#8208;tolerant <I>Propionibacterium acidipropionici</I> to reveal the microbial response of cells to acid stress during fermentation. Combined with the results of previous proteomic and metabolomic studies, several potential acid&#8208;resistance mechanisms of <I>P. acidipropionici</I> were analyzed. Energy metabolism and transporter activity of cells were regulated to maintain pH homeostasis by balancing transmembrane transport of protons and ions; redundant protons were eliminated by enhancing the metabolism of certain amino acids for a relatively stable intracellular microenvironment; and protective mechanism of macromolecules were also induced to repair damage to proteins and DNA by acids. Transcriptomic data indicated that the synthesis of acetate and lactate were undesirable in the acid&#8208;resistant mutant, the expression of which was 2.21&#8208;fold downregulated. In addition, metabolomic data suggested that the accumulation of lactic acid and acetic acid reduced the carbon flow to PA and led to a decrease in pH. On this basis, we propose a metabolic engineering strategy to regulate the synthesis of lactic acid and acetic acid that will reduce by&#8208;products significantly and increase the PA yield by 12.2% to 10.31 &plusmn; 0.84 g/g DCW. Results of this study provide valuable guidance to understand the response of bacteria to acid stress and to construct microbial cell factories to produce organic acids by combining systems biology technologies with synthetic biology tools.</P>

2018

0006-3592

1097-0290

115

2

pp.483-494

10.1002/bit.26478

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART79345140

acid resistance; genomics; metabolic engineering; Propionibacterium acidipropionici; transcriptomics