scholarly journals Biosynthesis ofcis,cis-Muconic Acid and Its Aromatic Precursors, Catechol and Protocatechuic Acid, from Renewable Feedstocks by Saccharomyces cerevisiae

2012 ◽  
Vol 78 (23) ◽  
pp. 8421-8430 ◽  
Author(s):  
Christian Weber ◽  
Christine Brückner ◽  
Sheila Weinreb ◽  
Claudia Lehr ◽  
Christine Essl ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Adipic Acid ◽  
Aromatic Amino Acid ◽  
Protocatechuic Acid ◽  
Amino Acid Biosynthesis ◽  
Biosynthesis Pathway ◽  
Acid Biosynthesis ◽  
Muconic Acid ◽  
Production Processes

ABSTRACTAdipic acid is a high-value compound used primarily as a precursor for the synthesis of nylon, coatings, and plastics. Today it is produced mainly in chemical processes from petrochemicals like benzene. Because of the strong environmental impact of the production processes and the dependence on fossil resources, biotechnological production processes would provide an interesting alternative. Here we describe the first engineeredSaccharomyces cerevisiaestrain expressing a heterologous biosynthetic pathway converting the intermediate 3-dehydroshikimate of the aromatic amino acid biosynthesis pathway via protocatechuic acid and catechol intocis,cis-muconic acid, which can be chemically dehydrogenated to adipic acid. The pathway consists of three heterologous microbial enzymes, 3-dehydroshikimate dehydratase, protocatechuic acid decarboxylase composed of three different subunits, and catechol 1,2-dioxygenase. For each heterologous reaction step, we analyzed several potential candidates for their expression and activity in yeast to compose a functionalcis,cis-muconic acid synthesis pathway. Carbon flow into the heterologous pathway was optimized by increasing the flux through selected steps of the common aromatic amino acid biosynthesis pathway and by blocking the conversion of 3-dehydroshikimate into shikimate. The recombinant yeast cells finally produced about 1.56 mg/litercis,cis-muconic acid.

Computational investigations of allostery in aromatic amino acid biosynthetic enzymes

2021 ◽  
Author(s):  
Wanting Jiao
Keyword(s):  
Amino Acid ◽  
Aromatic Amino Acid ◽  
Amino Acid Biosynthesis ◽  
Chorismate Mutase ◽  
Tryptophan Synthase ◽  
Biosynthesis Pathway ◽  
Acid Biosynthesis ◽  
Computational Tools ◽  
Aromatic Amino Acid Biosynthesis ◽  
Allosteric Mechanisms

Allostery, in which binding of ligands to remote sites causes a functional change in the active sites, is a fascinating phenomenon observed in enzymes. Allostery can occur either with or without significant conformational changes in the enzymes, and the molecular basis of its mechanism can be difficult to decipher using only experimental techniques. Computational tools for analyzing enzyme sequences, structures, and dynamics can provide insights into the allosteric mechanism at the atomic level. Combining computational and experimental methods offers a powerful strategy for the study of enzyme allostery. The aromatic amino acid biosynthesis pathway is essential in microorganisms and plants. Multiple enzymes involved in this pathway are sensitive to feedback regulation by pathway end products and are known to use allostery to control their activities. To date, four enzymes in the aromatic amino acid biosynthesis pathway have been computationally investigated for their allosteric mechanisms, including 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, anthranilate synthase, chorismate mutase, and tryptophan synthase. Here we review the computational studies and findings on the allosteric mechanisms of these four enzymes. Results from these studies demonstrate the capability of computational tools and encourage future computational investigations of allostery in other enzymes of this pathway.

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