Recent Advances in Microbial Production of cis,cis-Muconic Acid

Abstract

cis,cis-Muconic acid (MA) is a valuable C6 dicarboxylic acid platform chemical that is used as a starting material for the production of various valuable polymers and drugs, including adipic acid and terephthalic acid. As an alternative to traditional chemical processes, bio-based MA production has progressed to the establishment of de novo MA pathways in several microorganisms, such as Escherichia coli, Corynebacterium glutamicum, Pseudomonas putida, and Saccharomyces cerevisiae. Redesign of the metabolic pathway, intermediate flux control, and culture process optimization were all pursued to maximize the microbial MA production yield. Recently, MA production from biomass, such as the aromatic polymer lignin, has also attracted attention from researchers focusing on microbes that are tolerant to aromatic compounds. This paper summarizes recent microbial MA production strategies that involve engineering the metabolic pathway genes as well as the heterologous expression of some foreign genes involved in MA biosynthesis. Microbial MA production will continue to play a vital role in the field of bio-refineries and a feasible way to complement various petrochemical-based chemical processes.

Keywords: cis,cis-Muconic acid; metabolic engineering; microbial production; shikimate pathway.

Figure 1

Schematic overview of the metabolic pathway for MA biosynthesis in E. coli. The red arrow (pathway 1), purple arrow (pathway 2), tan arrow (pathway 3), brown arrow (pathway 4), blue arrow (pathway 5), and green arrow (pathway 6) represent MA biosynthetic pathways 1, 2, 3, 4, 5, and 6, respectively. G6P, glucose-6- phosphate; PPP, pentose phosphate pathway; PYR, pyruvate; PEP, phosphoenolpyruvate; E4P, erythrose4-phosphate; DAHP, 3-deoxy-D-arabinoheptulosonate-7-phosphate; DHS, 3-dehydroshikimate; SHK, shikimic acid; Phe, phenylalanine; Tyr, tyrosine; Trp, tryptophan; CHR, chorismate; 4-HBA, 4-hydroxybenzoate; IC, isochorismate; 2,3-DHB, 2,3-dihydroxybenzoate; SA, salicylate; PCA, protocatechuate; CA, catechol; MA, muconic acid. DAHPS, DAHP synthase; DHQS, DHQ synthase; DHQD, DHQ dehydratase; SDH, shikimate dehydrogenase; SK, shikimate kinase; EPSP-S, 5-enolpyruvylshikimate-3-phosphate synthase; CS, chorismate synthase; CM, chorismate mutase; AS, anthranilate synthase; DHSD, DHS dehydratase; PCA-DC, protocatechuate decarboxylase; CDO, catechol 1,2-dioxygenase; TPL, tyrosine phenol lyase; PH, phenol hydroxylase; CL, chorismate pyruvate-lyase; ICS, isochorismate synthase; IM, isochorismatase; DH-DHBAD, 2,3-dihydro-2,3-DHBA dehydrogenase; IPL, isochorismate pyruvate lyase; DBH-DC, 2,3-dihydroxybenzoate decarboxylase; SMO, salicylate 1-monoxygenase; ADO, anthranilate 1,2-dioxygenase.

Figure 2

Schematic overview of the aromatic compound degradation metabolic pathway in C. glutamicum for MA biosynthesis. G6P, glucose-6- phosphate; PPP, pentose phosphate pathway; PYR, pyruvate; PEP, phosphoenolpyruvate; E4P, erythrose4-phosphate; DAHP, 3-deoxy-D-arabinoheptulosonate-7-phosphate; DHS, 3-dehydroshikimate; SHK, shikimic acid; Phe, phenylalanine; Tyr, tyrosine; Trp, tryptophan; CHR, chorismate; 4-HBA, 4-hydroxybenzoate; IC, isochorismate; 2,3-DHB, 2,3 dihydroxybenzoate; SA, salicylate; PCA, protocatechuate; CA, catechol; MA, muconic acid. DAHPS, DAHP synthase; DHQS, DHQ synthase; DHQD, DHQ dehydratase; SDH, shikimate dehydrogenase; SK, shikimate kinase; EPSP-S, 5-enolpyruvylshikimate-3-phosphate synthase; CS, chorismate synthase; DHSD, DHS dehydratase; PCA-DC, protocatechuate decarboxylase; CDO, catechol 1,2-dioxygenase; MCI, muconate cycloisomerase; PCA-DO, protocatechuate 3,4-dioxygenase; FCS, feruloyl–CoA synthetase; ECH, enoyl–CoA hydratase/aldolase; VDH, vanillin dehydrogenase; HBH, p-hydroxybenzoate hydroxylase; VODM, vanillate O-demethylase: PH, phenol hydroxylase; BDO, benzoate dioxygenase; BDD, benzoate diol dehydrogenase.