Biosynthesis of C4-C8 3-Hydroxycarboxylic Acids from Glucose through the Inverted Fatty Acid β-Oxidation by Metabolically Engineered Escherichia coli .

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Escherichia coli*/metabolism ; Escherichia coli*/genetics ; Glucose*/metabolism ; Oxidation-Reduction* ; Fatty Acids*/metabolism ; Fatty Acids*/biosynthesis ; Metabolic Engineering* ; Carboxylic Acids*/metabolism; Escherichia coli Proteins/metabolism ; Escherichia coli Proteins/genetics

Inverted fatty acid β-oxidation represents a versatile biochemical platform for biosynthesis by the engineered microbial strains of numerous value-added chemicals from convenient and abundant renewable carbon sources, including biomass-derived sugars. Although, in recent years, significant progress has been made in the production through this pathway of n-alcohols, 1,3-diols, and carboxylic acids and its 2,3-unsaturated derivatives, the potential of the pathway for the biosynthesis of 3-hydroxycarboxylic acids remained almost undisclosed. In this study, we demonstrate the microaerobic production of even-chain-length C4-C8 3-hydroxycarboxylic acids from glucose through the inverted fatty acid β-oxidation by engineered E. coli strains. The notable accumulation of target compounds was achieved upon the strong constitutive expression of the genes atoB , fadA , fadB , fadE / fabI , and tesB , which code for the key enzymes catalysing reactions of aerobic fatty acid β-oxidation and thioesterase II, in strains devoid of mixed-acid fermentation pathways and lacking nonspecific thioesterase YciA. The best performing recombinants were able to synthesise up to 14.5 mM of 3-hydroxycarboxylic acids from glucose with a total yield of 0.34 mol/mol and a C4/C6/C8 ratio averaging approximately 63/28/9. The results provide a framework for the development of highly efficient strains and processes for the bio-based production of valuable 3-hydroxycarboxylates from renewable raw materials.

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22-14-00040 Russian Science Foundation

Keywords: 3-hydroxycarboxylic acids; Escherichia coli; fatty acid β-oxidation; glucose

IY9XDZ35W2 (Glucose)
0 (Fatty Acids)
0 (Carboxylic Acids)
0 (Escherichia coli Proteins)

Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240429

20240429

PMC11048500

10.3390/biom14040449

38672466