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Fatty Acid-Derived Biofuels and Chemicals Production in Saccharomyces cerevisiae.

Zhou YJ, Buijs NA, Siewers V, Nielsen J - Front Bioeng Biotechnol (2014)

Bottom Line: From an engineering perspective, the pathway for fatty acid biosynthesis is an attractive route for the production of advanced fuels such as fatty acid ethyl esters, fatty alcohols, and alkanes.The robustness and excellent accessibility to molecular genetics make the yeast Saccharomyces cerevisiae a suitable host for the purpose of bio-manufacturing.Recent advances in metabolic engineering, as well as systems and synthetic biology, have now provided the opportunity to engineer yeast metabolism for the production of fatty acid-derived fuels and chemicals.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology , Gothenburg , Sweden.

ABSTRACT
Volatile energy costs and environmental concerns have spurred interest in the development of alternative, renewable, sustainable, and cost-effective energy resources. Environment-friendly processes involving microbes can be used to synthesize advanced biofuels. These fuels have the potential to replace fossil fuels in supporting high-power demanding machinery such as aircrafts and trucks. From an engineering perspective, the pathway for fatty acid biosynthesis is an attractive route for the production of advanced fuels such as fatty acid ethyl esters, fatty alcohols, and alkanes. The robustness and excellent accessibility to molecular genetics make the yeast Saccharomyces cerevisiae a suitable host for the purpose of bio-manufacturing. Recent advances in metabolic engineering, as well as systems and synthetic biology, have now provided the opportunity to engineer yeast metabolism for the production of fatty acid-derived fuels and chemicals.

No MeSH data available.


Related in: MedlinePlus

Comparison of S. cerevisiae type I (A) and bacterial type II (B) fatty acid synthases is shown. (A) The catalytic reaction cycle of and domain organization of yeast fatty acid synthase. Acetyl-CoA is activated by ACP acyltransferase (AT) and then malonyl-CoA is iteratively fed into the reaction cycle by malonyl/palmitoyl transferase (MPT). The elongation process is consecutively catalyzed by ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). After several rounds of elongation, the end product is released from the enzyme as a fatty acyl-CoA after back-transfer to CoA from ACP by the double-functional MPT. Desaturation of fatty acyl-CoA takes place in the endoplasmic reticulum and is catalyzed by the Δ9-fatty acid desaturase Ole1, and very long-chain fatty acids (VLFA) are synthesized by chain elongation of saturated acyl-CoAs through a cyclic series of reactions reminiscent of fatty acid de novo synthesis. (B) Bacterial type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes. Acetoacetyl-ACP is in prior synthesized for the initiation of chain elongation, and then malonyl-CoA is iteratively fed into the elongation cycle after ACP loading, which is catalyzed by FabD. Desaturation can be performed at the C10 chain length by 3-hydroxydecanoyl-ACP dehydrase (FabA), and the product cis-3-enoyl acyl-ACP bypasses FabI of reduction and goes to FabB for the next round of elongation. Different from yeast fatty acid biosynthesis, the end product is released as a fatty acyl-ACP after several rounds of elongation.
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Figure 1: Comparison of S. cerevisiae type I (A) and bacterial type II (B) fatty acid synthases is shown. (A) The catalytic reaction cycle of and domain organization of yeast fatty acid synthase. Acetyl-CoA is activated by ACP acyltransferase (AT) and then malonyl-CoA is iteratively fed into the reaction cycle by malonyl/palmitoyl transferase (MPT). The elongation process is consecutively catalyzed by ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). After several rounds of elongation, the end product is released from the enzyme as a fatty acyl-CoA after back-transfer to CoA from ACP by the double-functional MPT. Desaturation of fatty acyl-CoA takes place in the endoplasmic reticulum and is catalyzed by the Δ9-fatty acid desaturase Ole1, and very long-chain fatty acids (VLFA) are synthesized by chain elongation of saturated acyl-CoAs through a cyclic series of reactions reminiscent of fatty acid de novo synthesis. (B) Bacterial type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes. Acetoacetyl-ACP is in prior synthesized for the initiation of chain elongation, and then malonyl-CoA is iteratively fed into the elongation cycle after ACP loading, which is catalyzed by FabD. Desaturation can be performed at the C10 chain length by 3-hydroxydecanoyl-ACP dehydrase (FabA), and the product cis-3-enoyl acyl-ACP bypasses FabI of reduction and goes to FabB for the next round of elongation. Different from yeast fatty acid biosynthesis, the end product is released as a fatty acyl-ACP after several rounds of elongation.

Mentions: The biosynthesis of fatty acids in S. cerevisiae differs from that in bacteria such as Escherichia coli (Figure 1). In bacteria, fatty acid synthesis is carried out by a type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes (Figure 1B); while in S. cerevisiae, the de novo synthesis of fatty acids can take place in at least two subcellular compartments: cytoplasm (type I FAS) and mitochondria (type II FAS). Mitochondrial FAS II has been implicated as the sole mitochondrial source of octanoic acid, which is a precursor of the lipoic acid (LA) cofactor that is required for maintaining the function of several mitochondrial enzyme complexes such as pyruvate dehydrogenase (Hiltunen et al., 2009). However, most functional and storage lipids are synthesized by cytosol type I FAS (Koch et al., 2014), which is a large, multifunctional dimeric complex that is responsible for fatty acid synthesis from malonyl-CoA and acetyl-CoA (Figure 1A). This distinction is important as it has implications for further metabolic engineering of fatty acid metabolism. Considering its predominant role for fatty acids synthesis, we will focus on the FAS I system. This process starts with loading of acetyl-CoA to the acyl carrier protein (ACP) by the ACP acyltransferase (AT). Then consecutive catalytic steps of β-ketoacyl-ACP synthesis, β-ketoacyl-ACP reduction, β-hydroxyacyl-ACP dehydration, and enoyl-ACP reduction extend the chain length in a repetitive manner by using malonyl-CoA as building blocks. The malonyl-CoA is synthesized from acetyl-CoA by incorporation of CO2, which is catalyzed by acetyl-CoA carboxylase (Acc1). The chain extension usually stops at palmitoyl-ACP after seven cycles, which is mainly determined by the ketoacyl synthase domain (Sangwallek et al., 2013). Finally, acyl-ACP and malonyl-CoA are transformed by malonyl transacylase (MPT) to form acyl-CoA and the activated malonyl-ACP, which is necessary for initiating the next acyl-CoA synthesis. Acyl-CoA can be transformed into lipids or FFAs catalyzed by AT or thioesterase, respectively.


Fatty Acid-Derived Biofuels and Chemicals Production in Saccharomyces cerevisiae.

Zhou YJ, Buijs NA, Siewers V, Nielsen J - Front Bioeng Biotechnol (2014)

Comparison of S. cerevisiae type I (A) and bacterial type II (B) fatty acid synthases is shown. (A) The catalytic reaction cycle of and domain organization of yeast fatty acid synthase. Acetyl-CoA is activated by ACP acyltransferase (AT) and then malonyl-CoA is iteratively fed into the reaction cycle by malonyl/palmitoyl transferase (MPT). The elongation process is consecutively catalyzed by ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). After several rounds of elongation, the end product is released from the enzyme as a fatty acyl-CoA after back-transfer to CoA from ACP by the double-functional MPT. Desaturation of fatty acyl-CoA takes place in the endoplasmic reticulum and is catalyzed by the Δ9-fatty acid desaturase Ole1, and very long-chain fatty acids (VLFA) are synthesized by chain elongation of saturated acyl-CoAs through a cyclic series of reactions reminiscent of fatty acid de novo synthesis. (B) Bacterial type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes. Acetoacetyl-ACP is in prior synthesized for the initiation of chain elongation, and then malonyl-CoA is iteratively fed into the elongation cycle after ACP loading, which is catalyzed by FabD. Desaturation can be performed at the C10 chain length by 3-hydroxydecanoyl-ACP dehydrase (FabA), and the product cis-3-enoyl acyl-ACP bypasses FabI of reduction and goes to FabB for the next round of elongation. Different from yeast fatty acid biosynthesis, the end product is released as a fatty acyl-ACP after several rounds of elongation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4150446&req=5

Figure 1: Comparison of S. cerevisiae type I (A) and bacterial type II (B) fatty acid synthases is shown. (A) The catalytic reaction cycle of and domain organization of yeast fatty acid synthase. Acetyl-CoA is activated by ACP acyltransferase (AT) and then malonyl-CoA is iteratively fed into the reaction cycle by malonyl/palmitoyl transferase (MPT). The elongation process is consecutively catalyzed by ketoacyl reductase (KR), dehydratase (DH), and enoyl reductase (ER). After several rounds of elongation, the end product is released from the enzyme as a fatty acyl-CoA after back-transfer to CoA from ACP by the double-functional MPT. Desaturation of fatty acyl-CoA takes place in the endoplasmic reticulum and is catalyzed by the Δ9-fatty acid desaturase Ole1, and very long-chain fatty acids (VLFA) are synthesized by chain elongation of saturated acyl-CoAs through a cyclic series of reactions reminiscent of fatty acid de novo synthesis. (B) Bacterial type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes. Acetoacetyl-ACP is in prior synthesized for the initiation of chain elongation, and then malonyl-CoA is iteratively fed into the elongation cycle after ACP loading, which is catalyzed by FabD. Desaturation can be performed at the C10 chain length by 3-hydroxydecanoyl-ACP dehydrase (FabA), and the product cis-3-enoyl acyl-ACP bypasses FabI of reduction and goes to FabB for the next round of elongation. Different from yeast fatty acid biosynthesis, the end product is released as a fatty acyl-ACP after several rounds of elongation.
Mentions: The biosynthesis of fatty acids in S. cerevisiae differs from that in bacteria such as Escherichia coli (Figure 1). In bacteria, fatty acid synthesis is carried out by a type II fatty acid synthase (FAS) that consists of discrete, monofunctional enzymes (Figure 1B); while in S. cerevisiae, the de novo synthesis of fatty acids can take place in at least two subcellular compartments: cytoplasm (type I FAS) and mitochondria (type II FAS). Mitochondrial FAS II has been implicated as the sole mitochondrial source of octanoic acid, which is a precursor of the lipoic acid (LA) cofactor that is required for maintaining the function of several mitochondrial enzyme complexes such as pyruvate dehydrogenase (Hiltunen et al., 2009). However, most functional and storage lipids are synthesized by cytosol type I FAS (Koch et al., 2014), which is a large, multifunctional dimeric complex that is responsible for fatty acid synthesis from malonyl-CoA and acetyl-CoA (Figure 1A). This distinction is important as it has implications for further metabolic engineering of fatty acid metabolism. Considering its predominant role for fatty acids synthesis, we will focus on the FAS I system. This process starts with loading of acetyl-CoA to the acyl carrier protein (ACP) by the ACP acyltransferase (AT). Then consecutive catalytic steps of β-ketoacyl-ACP synthesis, β-ketoacyl-ACP reduction, β-hydroxyacyl-ACP dehydration, and enoyl-ACP reduction extend the chain length in a repetitive manner by using malonyl-CoA as building blocks. The malonyl-CoA is synthesized from acetyl-CoA by incorporation of CO2, which is catalyzed by acetyl-CoA carboxylase (Acc1). The chain extension usually stops at palmitoyl-ACP after seven cycles, which is mainly determined by the ketoacyl synthase domain (Sangwallek et al., 2013). Finally, acyl-ACP and malonyl-CoA are transformed by malonyl transacylase (MPT) to form acyl-CoA and the activated malonyl-ACP, which is necessary for initiating the next acyl-CoA synthesis. Acyl-CoA can be transformed into lipids or FFAs catalyzed by AT or thioesterase, respectively.

Bottom Line: From an engineering perspective, the pathway for fatty acid biosynthesis is an attractive route for the production of advanced fuels such as fatty acid ethyl esters, fatty alcohols, and alkanes.The robustness and excellent accessibility to molecular genetics make the yeast Saccharomyces cerevisiae a suitable host for the purpose of bio-manufacturing.Recent advances in metabolic engineering, as well as systems and synthetic biology, have now provided the opportunity to engineer yeast metabolism for the production of fatty acid-derived fuels and chemicals.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology , Gothenburg , Sweden.

ABSTRACT
Volatile energy costs and environmental concerns have spurred interest in the development of alternative, renewable, sustainable, and cost-effective energy resources. Environment-friendly processes involving microbes can be used to synthesize advanced biofuels. These fuels have the potential to replace fossil fuels in supporting high-power demanding machinery such as aircrafts and trucks. From an engineering perspective, the pathway for fatty acid biosynthesis is an attractive route for the production of advanced fuels such as fatty acid ethyl esters, fatty alcohols, and alkanes. The robustness and excellent accessibility to molecular genetics make the yeast Saccharomyces cerevisiae a suitable host for the purpose of bio-manufacturing. Recent advances in metabolic engineering, as well as systems and synthetic biology, have now provided the opportunity to engineer yeast metabolism for the production of fatty acid-derived fuels and chemicals.

No MeSH data available.


Related in: MedlinePlus