Metabolic Engineering of Microbial Organic Acid Production

Summary

Microbial organic acids such as malic, succinic, fumaric and polymalic acids have emerged as versatile platform chemicals for the food, pharmaceutical and polymer industries. Metabolic engineering harnesses genetic and process tools to reroute cellular pathways towards overproduction of these acids from renewable feedstocks. Key strategies include optimisation of biosynthetic enzymes, elimination of competing pathways, fine-tuning of regulatory circuits and enhancement of transport systems for efficient secretion. Host selection spans filamentous fungi, yeasts and bacteria, each offering distinct advantages in pathway capacity, tolerance and scalability. Advances in adaptive laboratory evolution, genome-scale modelling and synthetic biology have enabled dramatic improvements in titres, yields and productivities. Despite this progress, challenges remain in balancing growth and production, overcoming inhibitory compounds in lignocellulosic hydrolysates, and developing robust downstream processes. Continued integration of systems biology with process engineering promises to advance sustainable, large-scale manufacture of bio-based organic acids.

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Metabolic Engineering of Microbial Organic Acid Production publication trend

The graph below shows the total number of articles in metabolic engineering of microbial organic acid production across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolic engineering: The directed modification of cellular pathways to enhance production of a target metabolite.

Organic acid: A carboxylic acid (e.g. malic, succinic, fumaric) produced by microbial fermentation and used as a platform chemical.

Biosynthetic pathway: A series of enzymatic reactions within a cell that convert substrates into desired products.

Host strain: The microbial organism (bacterium, yeast or fungus) selected for genetic and process optimisation to produce the target compound.

Adaptive laboratory evolution: A method that applies selective pressure over many generations to enrich strains with desirable phenotypes.

Titre: The concentration of product (e.g. acid) accumulated in the fermentation broth, typically expressed in g L⁻¹.

References

  1. Microbial L-malic acid production: History, current progress, and perspectives. Green Carbon (2023).
  2. Engineering growth phenotypes of Aspergillus oryzae for L-malate production. Bioresources and Bioprocessing (2023).
  3. Efficient polymalic acid production from corn straw hydrolysate by detoxification of phenolic inhibitors. Frontiers in Bioengineering and Biotechnology (2023).
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