Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of treating or preventing autoimmune disorders, inhibiting inflammatory mechanisms in the gut, and/or tightening gut mucosal barrier function are disclosed.

The present invention relates to 25 hitherto undescribed genes of B. licheniformis and gene products derived thereform and all sufficiently homologous nucleic acids and proteins thereof. They occur in five different metabolic pathways for the formation of odorous substances. The metabolic pathways in question are for the synthesis of: 1) isovalerian acid (as part of the catabolism of leucine), 2) 2-methylbutyric acid and/or isobutyric acid (as part of the catabolism of valine and/or isoleucine), 3) butanol and/or butyric acid (as part of the metabolism of butyric acid), 4) propyl acid (as part of the metabolism of propionate) and/or 5) cadaverine and/or putrescine (as parts of the catabolism of lysine and/or arginine). The identification of these genes allows biotechnological production methods to be developed that are improved to the extent that, to assist these nucleic acids, the formation of the odorous substances synthesised via these metabolic pathways can be reduced by deactivating the corresponding genes in the micro-organism used for the biotechnological production. In addition, these gene products are thus available for preparing reactions or for methods according to their respective biochemical properties.

The present invention relates to a microorganism having an acetyl CoA biosynthesis pathway and a butyryl CoA biosynthesis pathway; the microorganism being a recombinant microorganism having an increased ability to produce butanol, wherein a pathway for converting acetyl CoA into acetate is suppressed, and a pathway for converting acetate into acetyl CoA and a pathway for converting butyryl CoA into butanol are promoted. Also, the present invention concerns a method for producing butanol by using the recombinant microorganism.

A genetically engineered strain of Escherichia coli Nissle 1917 (EcN) with a modified genome designed to enhance the production of short-chain fatty acids (SCFAs) is provided. The engineered genome includes the atoB gene from E. coli K-12, responsible for encoding acetyl-CoA acetyltransferase, a crt-bcd-etfA-etfB-BHBD gene cluster from E. C. butyricum that encodes enzymes involved in the synthesis of SCFAs, specifically enoyl-CoA hydratase, butyryl-CoA dehydrogenase, and electron transfer flavoproteins, and the ptb-buk gene from C. acetobutyricum, which encodes phosphotransbutyrylase and butyrate kinase. Additionally, key genes associated with competing metabolic pathwaysldhA, frdABCD, adhE, ackA, and ptaare deleted to optimize SCFA production, particularly butyrate. This strain is intended for use in therapeutic applications where enhanced SCFA production is beneficial, such as in the treatment of coronary heart disease.

The present invention relates to a recombinant organism or microorganism having a decreased pool of crotonic acid compared to the organism or microorganism from which it is derived due to at least one of: (i) an increased conversion of crotonyl-CoA into butyryl-CoA; and/or an increased conversion of butyryl-CoA into butyric acid; (ii) an increased conversion of crotonyl-CoA into 3-hydroxybutyryl-CoA; and/or an increased conversion of 3-hydroxybutyryl-CoA into 3-hydroxybutyric acid; (iii) an increased conversion of crotonic acid into crotonyl-CoA; (iv) an increased conversion of crotonyl-[acyl-carrier protein] into butyryl [acyl-carrier-protein]; (v) a decreased conversion of crotonyl-CoA into crotonic acid; and/or (vi) a decreased conversion of crotonyl-[acyl-carrier protein] into crotonic acid. Moreover, the present invention relates to the use of such a recombinant organism or microorganism for the production of alkenes with the enzyme ferulic acid decarboxylase. Further, the present invention relates to a method for the production of isobutene or butadiene by culturing such a recombinant organism or microorganism in a suitable culture medium under suitable conditions.

Described is a recombinant organism or microorganism which is capable of enzymatically converting acetyl-CoA into isobutene, (A) wherein in said organism or microorganism: (i) acetyl-CoA is enzymatically converted into acetoacetyl-CoA, (ii) acetoacetyl-CoA is enzymatically converted into 3-hydroxy-3-methylglutaryl-CoA, (iii) 3-hydroxy-3-methylglutaryl-CoA is enzymatically converted into 3-methylglutaconyl-CoA, (iv) 3-methylglutaconyl-CoA is enzymatically converted into 3-methylcrotonyl-CoA, and (v) wherein said 3-methylcrotonyl-CoA is converted into isobutene by: (a) enzymatically converting 3-methylcrotonyl-CoA into 3-methylcrotonic acid which is then further enzymatically converted into said isobutene; or (b) enzymatically converting 3-methylcrotonyl-CoA into 3-hydroxy-3-methylbutyryl-CoA which is then further enzymatically converted into 3-hydroxy-3-methylbutyric acid which is then further enzymatically converted into 3-phosphonoxy-3-methylbutyric acid which is then further enzymatically converted into said isobutene; (B) wherein said recombinant organism or microorganism has an increased pool of coenzyme A (CoA) over the organism or microorganism from which it is derived due to: (i) an increased uptake of pantothenate; and/or (ii) an increased conversion of pantothenate into CoA. Moreover, described is the use of such a recombinant organism or microorganism for the production of isobutene. Further, described is a method for the production of isobutene by culturing such a recombinant organism or microorganism in a suitable culture medium under suitable conditions.

Microorganisms are genetically engineered to continuously produce fatty acids, fatty alcohols, cultured protein, or any combination thereof by microbial fermentation, particularly by microbial fermentation of a gaseous substrate. The microorganisms are C1-fixing. The production of fatty acids, fatty alcohols, and cultured proteins can be improved. This can be improved through the expression of 3-hydroxyacyl-ACP:CoA transacylases.