The present disclosure is directed to the biosynthetic pathway for a nonribosomal peptide synthetase (NRPS) derived drug and analogs thereof. The invention provides polynucleotide sequences useful for heterologous expression in a convenient microbial host for the synthesis of the NRPS-derived drug, the polypeptides encoded by such polynucleotides, expression vectors comprising the polynucleotides, host cells comprising the polynucleotides or expression vectors, and kits comprising a host cell. Also provided is a method for the production of ET-743, the NRPS-derived drug.

The present invention concerns a metabolically engineered microorganism for glycine bioproduction or a salt or an ester thereof, the genome of said microorganism comprises an attenuation of the expression of genes encoding enzymes having glycine cleavage system activity as defined by E.C. 1.4.1.27 together with an overexpressing of threonine dehydrogenase dependent pathway as defined by EC E.C. 1.1.1.103 and E.C. 2.3.1.29 and/or with a threonine aldolase dependent pathway as defined by E.C. 4.1.2.48 or EC 4.1.2.42 or any of its catalytically active variants, its use for the production of glycine or one of its salts or esters. The present invention also concerns a fermentation process using said metabolically engineered microorganism for the production of glycine or one of its salts or esters.

Disclosed is a novel genetically modified microorganism showing improved yields of 3-hydroxyadipic acid and/or -hydromuconic acid. The genetically modified microorganism is a microorganism having an ability to produce 3-hydroxyadipic acid and/or -hydromuconic acid, in which the reaction to generate malic acid from oxaloacetic acid is enhanced, and the reaction to generate acetyl-CoA from pyruvic acid is enhanced. In addition, the reaction to generate carbon dioxide from formic acid is enhanced.

The disclosure provides a metabolic pathway for producing a metabolite, the metabolic pathway having a co-factor purge valve system for recycling a cofactor used in the metabolic pathway.

The present invention relates to a genetically engineered microorganism expressing (i) formate tetrahydrofolate (THF) ligase, methenyi-THF cyclohydrolase and methylene-THF dehydrogenase, (ii) the enzymes of the glycine cleavage system (GCS), (iii) serine deaminase and serine hydroxymethyltransferase (SHMT), (iv) an enzyme increasing the availability of NADPH, and (v) optionally formate dehydrogenase (FDH), and wherein the genetically engineered microorganism has been genetically engineered to express at least one of the enzymes of (i) to (v), wheren said enzyme is not expressed by the corresponding microorganism that has been used to prepare the genetically engineered microorganism, and wherein the enzymes of (i) to (v) are genomically expressed.