The invention relates to a method of cell culture where the cells are modified to reduce the level of synthesis of growth and/or productivity inhibitors by the cell. The invention also relates to a method of cell culture for improving cell growth and productivity, in particular in fed-batch culture of mammalian cells at high cell density. The invention further relates to a method of producing cells with improved cell growth and/or productivity in cell culture and to cells obtained or obtainable by such methods.

A method for the use of a cytochrome P450 enzyme comprising any of SEQ ID NO: 1-118, or mutants thereof or a variant enzyme having at least 70% identity thereto and having CYP450 activity, for the hydroxylation and or dealkylation of an organic compound.

##STR00001## ##STR00002## ##STR00003## ##STR00004##

The present disclosure provides engineered transaminase polypeptides useful for the synthesis of chiral amine compounds under industrially relevant conditions. The disclosure also provides polynucleotides encoding the engineered transaminase polypeptides, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases for the production of chiral amine compounds.

The present disclosure includes a construct comprising a leupeptin biosynthesis operon, the operon comprising leupA, leupB, leupC, and leupD genes operably linked to a promoter. Also included are cells comprising the construct, and methods for production of leupeptin peptide.

Aspects of the invention include host cells that are engineered to produce benzylisoquinoline alkaloids (BIAs). The host cells include heterologous coding sequences for a variety of enzymes involved in synthetic pathways from starting compounds to BIAs of the host cell. Also provided are methods of producing the BIAs of interest by culturing the host cells under culture conditions that promote expression of enzymes encoded by the heterologous coding sequences of the host cells. Aspects of the invention further include compositions, e.g., host cells, starting compounds and kits, etc., that find use in methods of the invention.

The present invention provides triazolone compounds of general formula (I): ##STR00001##
in which R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

The present disclosure provides a bioprocess for the simultaneous production of Polyhydroxybutyrate (PHB) and Violacein pigment in a single fermentation using a Himalayan bacterial isolate Iodobacter sp. PCH 194, having accession number MTCC 25171. PHB has plastic properties, renewable origin and bio-degradable nature. It can be used for various packaging applications replacing the petrochemicals-based plastics, thus providing greener alternative to environment. Violacein pigment has anti-oxidant, anti-tumoral, anti-bacterial, and photo-protective properties and can be used in cosmetics and pharmaceuticals applications. The present disclosure provides production process of two valuable products i.e. PHB and violacein pigment in a single bioprocess, therefore, is economically attractive, time saving, and commercially feasible process.

The present invention provides engineered ketoreductase and phosphite dehydrogenase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase and phosphite dehydrogenase enzymes, as well as polynucleotides encoding the engineered ketoreductase and phosphite dehydrogenase enzymes, host cells capable of expressing the engineered ketoreductase and phosphite dehydrogenase enzymes, and methods of using the engineered ketoreductase and phosphite dehydrogenase enzymes to synthesize a chiral catalyst used in the synthesis of antiviral compounds, such as nucleoside inhibitors. The present invention further provides methods of using the engineered enzymes to deracemize a chiral alcohol in a one-pot, multi-enzyme system.

Nodulisporic acids (NAs) comprise a group of indole diterpenes known for their potent insecticidal activities; however, biosynthesis of NAs by its natural producer, Hypoxylon pulicicidum (Nodulisporium sp.) is exceptionally difficult to achieve. The identification of genes responsible for NA production could enable biosynthetic pathway optimization to provide access to NAs for commercial applications. Obtaining useful quantities of NAs using published fermentations methods is challenging, making gene knockout studies an undesirable method to confirm gene function. Alternatively, heterologous gene expression of H. pulicicidum genes in a more robust host species like Penicillium paxilli provides a way to rapidly identify the function of genes that play a role in NA biosynthesis. In this work, we identified the function of four secondary-metabolic genes necessary for the biosynthesis of nodulisporic acid F (NAF) and reconstituted these genes in the genome of P. paxilli to enable heterologous production of NAF in this fungus.

A method of producing a catalytic carbon fiber may include: providing a carbon fiber and an aminated macrocycle, mixing the carbon fiber and the aminated macrocycle with a solvent; and reacting the carbon fiber and the aminated macrocycle to form an amide bond between the carbon fiber and the aminated macrocycle thereby forming the catalytic carbon fiber.