The present invention provides biochemical pathways, glyoxylate producing recombinant microorganisms, and methods for the production and yield improvement of glycolic acid and/or glycine via a reverse glyoxylate shunt. The reverse glyoxylate shunt comprises an enzyme that catalyzes the carboxylation of phosphoenol pyruvate (PEP) to oxaloacetate (OAA), or an enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate (OAA) or an enzyme that catalyzes the carboxylation of pyruvate to malate or a combination of any of the previous reactions; an enzyme that catalyzes the conversion of malate to malyl-CoA; an enzyme that catalyzes the conversion of malyl-CoA to glyoxylate and acetyl-CoA; and optionally an enzyme that catalyzes the conversion of oxaloacetate (OAA) to malate. Glyoxylate is reduced to produce glycolate. Alternatively, glyoxylate is converted to glycine. The reverse glyoxylate shunt pathway of the present invention can be utilized synergistically with other glycolic acid and/or glycine producing pathways to increase product yield.

A method for constructing an ALA production bacterial strain, the method enhances the activity of related enzymes promoting the synthesis of oxaloacetate and in the 5-aminolevulinic acid (ALA) production bacterial strain, or introducing exogenous related enzymes promoting the synthesis of oxaloacetate, such as phosphoenolpyruvate carboxylase or pyruvate carboxylase, and/or reducing the activity of related enzymes in the downstream metabolic pathway of succinyl coenzyme A in the bacterial strain, such as succinyl coenzyme A synthetase or succinate dehydrogenase, and/or reducing the activity of phosphoenolpyruvate carboxylated kinase and/or malic enzyme. An ALA high-yield bacterial strain constructed by utilizing the method, and method for utilizing the bacterial strain to prepare ALA.

The present disclosure provides use of malic enzyme 2 (ME2) in preparation of a diagnostic reagent or a medicament for silicosis or pulmonary fibrosis-related diseases, and belongs to the technical fields of medical treatment and medicine. Research results of the present disclosure show that ME2 knockout significantly alleviates inflammatory response and fibrotic lesions in mice with silicosis. Based on the above research results, the present disclosure provides use of ME2 in treatment of pulmonary inflammatory responses and pulmonary fibrotic lesions of silicosis or pulmonary fibrosis-related diseases. Expression of ME2 is inhibited to alleviate the inflammatory response and fibrotic lesions of the silicosis, providing support for exploring a targeted drug for treating pulmonary inflammatory responses and pulmonary fibrosis of silicosis or pulmonary fibrosis-related diseases.

The present invention provides biochemical pathways, glyoxylate producing recombinant microorganisms, and methods for the production and yield improvement of glycolic acid and/or glycine via a reverse glyoxylate shunt. The reverse glyoxylate shunt comprises an enzyme that catalyzes the carboxylation of phosphoenol pyruvate (PEP) to oxaloacetate (OAA), or an enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate (OAA) or an enzyme that catalyzes the carboxylation of pyruvate to malate or a combination of any of the previous reactions; an enzyme that catalyzes the conversion of malate to malyl-CoA; an enzyme that catalyzes the conversion of malyl-CoA to glyoxylate and acetyl-CoA; and optionally an enzyme that catalyzes the conversion of oxaloacetate (OAA) to malate. Glyoxylate is reduced to produce glycolate. Alternatively, glyoxylate is converted to glycine. The reverse glyoxylate shunt pathway of the present invention can be utilized synergistically with other glycolic acid and/or glycine producing pathways to increase product yield.

Provided is a mutant filamentous fungus having improved C4 dicarboxylic acid productivity and a method for producing a C4 dicarboxylic acid using the mutant filamentous fungus. A mutant filamentous fungus having enhanced expression of at least one polypeptide selected from the group consisting of a polypeptide consisting of the amino acid sequence represented by SEQ ID No: 2; a polypeptide consisting of an amino acid sequence having an identity of at least 90% with the amino acid sequence represented by SEQ ID No: 2 and having malic enzyme activity; and a polypeptide consisting of an amino acid sequence having deletion, substitution, addition or insertion of one or more amino acids with respect to the amino acid sequence represented by SEQ ID No: 2 and having malic enzyme activity.