Opportunities and Challenges for Microbial Synthesis of Fatty Acid-Derived Chemicals (FACs)

Liu, Yilan; Benitez, Mauricio Garcia; Chen, Jinjin; Harrison, Emma; Khusnutdinova, Anna N.; Mahadevan, Radhakrishnan

doi:10.3389/fbioe.2021.613322

Cited by 6 publications

(2 citation statements)

References 149 publications

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“…Free fatty acids (FFAs) are essential precursors for the synthesis of alkanes, fatty alcohols, fatty acid alkyl esters, and other fatty acid-derived chemicals (FACs), which have wide applications in biofuels, pharmaceuticals, feed additives, and others [ 1 , 2 ]. In recent years, FFAs production via metabolically engineered microbes has become a green and promising alternative to conventional extraction methods based on petroleum or plant biomass [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

Fang,

Han,

Feng

et al. 2024

Synthetic and Systems Biotechnology

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Section: Introductionmentioning

confidence: 99%

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

Fang,

Han,

Feng

et al. 2024

Synthetic and Systems Biotechnology

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“…Escherichia coli, Saccharomyces cerevisiae, and oleaginous yeasts like Yarrowia lipolytica and Rhodosporidium toruloides are commonly utilized microbial chassis in engineering approaches for optimized FA production [5,9,10]. E. coli has been intensively investigated in regard to its fatty acid biosynthesis and regulation [11,12].…”

Section: Introductionmentioning

confidence: 99%

Tuning Fatty Acid Profile and Yield in Pichia pastoris

Kobalter,

Voit,

Bekerle-Bogner

et al. 2023

Bioengineering

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Fatty acids have been supplied for diverse non-food, industrial applications from plant oils and animal fats for many decades. Due to the massively increasing world population demanding a nutritious diet and the thrive to provide feedstocks for industrial production lines in a sustainable way, i.e., independent from food supply chains, alternative fatty acid sources have massively gained in importance. Carbohydrate-rich side-streams of agricultural production, e.g., molasses, lignocellulosic waste, glycerol from biodiesel production, and even CO2, are considered and employed as carbon sources for the fermentative accumulation of fatty acids in selected microbial hosts. While certain fatty acid species are readily accumulated in native microbial metabolic routes, other fatty acid species are scarce, and host strains need to be metabolically engineered for their high-level production. We report the metabolic engineering of Pichia pastoris to produce palmitoleic acid from glucose and discuss the beneficial and detrimental engineering steps in detail. Fatty acid secretion was achieved through the deletion of fatty acyl-CoA synthetases and overexpression of the truncated E. coli thioesterase ‘TesA. The best strains secreted >1 g/L free fatty acids into the culture medium. Additionally, the introduction of C16-specific ∆9-desaturases and fatty acid synthases, coupled with improved cultivation conditions, increased the palmitoleic acid content from 5.5% to 22%.

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The β‐Ketoacyl‐ACP Synthase FabF Catalyzes Carbon‐Carbon Bond Formation in a Bimodal Pattern for Fatty Acid Biosynthesis

Huang,

Wang,

Cai

et al. 2024

Angewandte Chemie

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Fatty acids produced by the type‐II fatty acid biosynthesis pathway (FAS‐II) are essential biomaterials for bacterial membrane construction and numerous metabolic routes. The β‐ketoacyl‐ACP synthase FabF catalyzes the key C‐C bond formation step for fatty acid extension in FAS‐II. Here, we revealed the substrate recognition and catalytic mechanisms of FabF by determining FabF‐ACP complexes. FabF displays a distinctive bimodal catalytic pattern specifically on C6 and C10 acyl‐ACP substrates. It utilizes positively charged residues located on the η3‐helix and loop1 regions near the catalytic tunnel entrance to bind ACP, and two hydrophobic cavities as well as “front”, “middle”, and “back” door residues to specifically stabilize C6 and C10 acyl substrates for preferential catalysis. Further quantum chemistry calculations suggest that the FabF catalytic residues Lys336 and His304 facilitate proton transfer during condensation catalysis and C‐C bond formation. Our results provide key mechanistic insights into the biosynthesis of molecular carbon skeletons based on ketosynthases that are highly conserved through the FAS and polyketide synthase (PKS) analogous biosynthetic routes, broaden the understanding of the tricarboxylic acid cycle that utilizes lipoic acid derived from C8‐ACP accumulated due to the FabF distinctive catalytic pattern for oxidative decarboxylations, and may facilitate the development of narrow‐spectrum antibacterial drugs.

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Opportunities and Challenges for Microbial Synthesis of Fatty Acid-Derived Chemicals (FACs)

Cited by 6 publications

References 149 publications

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

Tuning Fatty Acid Profile and Yield in Pichia pastoris

The β‐Ketoacyl‐ACP Synthase FabF Catalyzes Carbon‐Carbon Bond Formation in a Bimodal Pattern for Fatty Acid Biosynthesis

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