Microbial acetyl-CoA metabolism and metabolic engineering

• Published in: Metabolic engineering Vol. 28; pp. 28 - 42
• Main Authors: Krivoruchko, Anastasia, Zhang, Yiming, Siewers, Verena, Chen, Yun, Nielsen, Jens
• Format: Journal Article
• Language: English
• Published: Belgium Elsevier Inc 01.03.2015
• Subjects: Acetyl Coenzyme A - biosynthesis; Acetyl Coenzyme A - genetics; Acetyl-CoA; Bacteria; Central carbon metabolism; Escherichia coli - genetics; Escherichia coli - metabolism; Industrial biotechnology; Metabolic Engineering; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Yeast; Yeast; A-ALD; FBA; RTG; ADH; UAS; FPP; PHA; FNR; PHB; TPI; acetyl-AMP; PDC; PNO; HMGR; SDPADS; PDH; PFL; URS; Bacteria; Industrial biotechnology; ACC; MS; ACK; Central carbon metabolism; ACL; Acetyl-CoA; ICRE; CS; ACS; HAP; CAT; POX; ALD; HAT; PFL-AE; FAEE; PK; CSRE; PFOR; PTA; HDAC
• DOI: 10.1016/j.ymben.2014.11.009
• ISSN: 1096-7176; 1096-7184

Recent concerns over the sustainability of petrochemical-based processes for production of desired chemicals have fueled research into alternative modes of production. Metabolic engineering of microbial cell factories such as Saccharomyces cerevisiae and Escherichia coli offers a sustainable and flexible alternative for the production of various molecules. Acetyl-CoA is a key molecule in microbial central carbon metabolism and is involved in a variety of cellular processes. In addition, it functions as a precursor for many molecules of biotechnological relevance. Therefore, much interest exists in engineering the metabolism around the acetyl-CoA pools in cells in order to increase product titers. Here we provide an overview of the acetyl-CoA metabolism in eukaryotic and prokaryotic microbes (with a focus on S. cerevisiae and E. coli), with an emphasis on reactions involved in the production and consumption of acetyl-CoA. In addition, we review various strategies that have been used to increase acetyl-CoA production in these microbes. •Many biotechnology products are derived from acetyl-CoA.•We review microbial acetyl-CoA metabolism with emphasis on S. cerevisiae and E. coli.•Recent years saw advances in engineering of microbial acetyl-CoA metabolism.•Some challenges in engineering of acetyl-CoA metabolism remain, particularly in the case of yeast.