The present invention provides for a genetically modified yeast cell comprising at least six or more of the following modifications: increased expression of Mus musculus fatty acid reductase, acetyl-CoA carboxylase, fatty acid synthase 1, fatty acid synthase 2, a mutant of the bottleneck enzyme encoded by ACC1 insensitive to post-transcriptional and post-translational repression, and/or a desaturase encoded by OLE1, and reduced expression of DGA1, HFD1, ADH6, and/or GDH1. The present invention provides a method for constructing the genetically modified yeast cell, and a method for producing a fatty alcohol from the genetically modified yeast cell.

A coryneform bacteria cell with an increased provision of Malonyl-CoA compared to its archetype, wherein the regulation and/or expression of one or more of genes fasB, gltA, accBC and accD1, and/or the functionality of the enzyme encoded by each gene is modified in a targeted manner. The cell may have one or more targeted modifications, including reduced or eliminated functionality of the fatty acid synthase FasB, mutation or partial or complete deletion of the fatty acid synthase encoding gene fasB, and/or reduced functionality of the promoter operatively linked to the citrate synthase gene gtIA, among other targeted modifications.

This application relates to the field of neurodegenerative diseases, more particularly to the field of Parkinson's disease. In particular, the disclosure describes that inhibitors reducing FAS activity can be used for treatment of Parkinson's disease, in particular, the treatment of patients suffering from Parkinson's disease having loss of function mutations in PINK1 or PARKIN genes.

This disclosure concerns recombinant host organisms genetically modified with a polyunsaturated fatty acid (PUFA) synthase system and one or more accessory proteins that allow for and/or improve the production of PUFAs in the host organism. The disclosure also concerns methods of making and using such organisms as well as products obtained from such organisms.

This application relates to the field of neurodegenerative diseases, more particularly to the field of Parkinson's disease. In particular, the disclosure describes that inhibitors reducing FAS activity can be used for treatment of Parkinson's disease, in particular, the treatment of patients suffering from Parkinson's disease having loss of function mutations in PINK1 or PARKIN genes.

The present invention provides for a genetically modified yeast cell comprising at least six or more of the following modifications: increased expression of Mus musculus fatty acid reductase, acetyl-CoA carboxylase, fatty acid synthase 1, fatty acid synthase 2, a mutant of the bottleneck enzyme encoded by ACC1 insensitive to post-transcriptional and post-translational repression, and/or a desaturase encoded by OLE1, and reduced expression of DGA1, HFD1, ADH6, and/or GDH1. The present invention provides a method for constructing the genetically modified yeast cell, and a method for producing a fatty alcohol from the genetically modified yeast cell.

Described herein are fusion proteins including methanol dehydrogenase (MeDH) and at least one other polypeptide such as 3-hexulose-6-phosphate dehydrogenase (HPS) or 6-phospho-3-hexuloisomerase (PHI), such as DHAS synthase or fructose-6-Phosphate aldolase or such as DHA synthase or DHA kinase. In a localized manner, the fusion protein can promote the conversion of methanol to formaldehyde and then to a ketose phosphate such as hexulose 6-phosphate or then to DHA and G3P. When expressed in cells, the fusion proteins can promote methanol uptake and rapid conversion to the ketose phosphate or to the DHA and D3P, which in turn can be used in a pathway for the production of a desired bioproduct. Beneficially, the rapid conversion to the ketose phosphate or to the DHA and G3P can avoid the undesirable accumulation of formaldehyde in the cell. Also described are engineered cells expressing the fusion protein, optionally include one or more additional metabolic pathway transgene(s), methanol metabolic pathway genes, target product pathway genes, cell culture compositions including the cells, methods for promoting production of the target product or intermediate thereof from the cells, compositions including the target product or intermediate, and products made from the target product or intermediate.

Among the various aspects of the present disclosure is the provision of a method of detection, treatment, and monitoring of cardiovascular disease or a foot wound by detection of a novel biomarker, Fatty Acid Synthase (FAS). Briefly, therefore, the present disclosure is directed to methods that allow for improved, noninvasive, and reliable diagnosis of these conditions, particularly in subjects suffering from Type 2 Diabetes (T2D).

Described herein are fusion proteins including methanol dehydrogenase (MeDH) and at least one other polypeptide such as 3-hexulose-6-phosphate dehydrogenase (HPS) or 6-phospho-3-hexuloisomerase (PHI), such as DHAS synthase or fructose-6-Phosphate aldolase or such as DHA synthase or DHA kinase. In a localized manner, the fusion protein can promote the conversion of methanol to formaldehyde and then to a ketose phosphate such as hexulose 6-phosphate or then to DHA and G3P. When expressed in cells, the fusion proteins can promote methanol uptake and rapid conversion to the ketose phosphate or to the DHA and D3P, which in turn can be used in a pathway for the production of a desired bioproduct. Beneficially, the rapid conversion to the ketose phosphate or to the DHA and G3P can avoid the undesirable accumulation of formaldehyde in the cell. Also described are engineered cells expressing the fusion protein, optionally include one or more additional metabolic pathway transgene(s), methanol metabolic pathway genes, target product pathway genes, cell culture compositions including the cells, methods for promoting production of the target product or intermediate thereof from the cells, compositions including the target product or intermediate, and products made from the target product or intermediate.

The present invention relates in a first aspect to a method for the purification of biological macromolecular complexes. Typically, no chromatography steps are applied. That is, the present invention relates to a method for the purification of biological macromolecular complexes Furthermore, the present invention relates to a method for crystallization of biological macromolecular complexes comprising the step of purification as described followed by crystallization in a reservoir solution containing a water-soluble polymer. Furthermore, purified biological macromolecular complexes obtainable by the method according to the present invention are provided as well as crystallized biological macromolecular complexes. Finally, a method for determining the suitability of a candidate compound for inhibiting the 20S proteasome of an individual is provided. Said method is particularly useful in personalized medicine identifying suitable inhibitors of the 20S proteasome in individuals for treating, ameliorating or preventing a cancer, an autoimmune disease, a muscular dystrophy, emphysema or cachexia accompanying cancer or AIDS.