Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called ‘cryptic’ or ‘silent’ pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.

The present invention relates to a carrier conjugate comprising at least one dodecin protein unit conjugated with at least one hapten and/or immunogenic and/or enzymatically active moiety. Further, the invention relates to a method for producing said conjugate and a method for producing antibodies that specifically binds to a hapten and/or immunogenic moiety of the conjugate, and to a method for performing enzymatic or diagnostic assays in vitro using said conjugate. Moreover, the invention relates to the use of said conjugate for producing antibodies that specifically bind to the epitope or epitopes contained in the moiety of said conjugate and use of said conjugate for performing enzymatic or diagnostic assays in vitro.

The invention pertains to host cells for producing a bioconjugate of an E. coli O18 antigen polysaccharide conjugated to a carrier protein. The host cells are characterized in that they comprise modified Wzy O-antigen polymerases with specific combinations of amino acid substitutions in one or more of positions 199, 377 and 395 as compared to the wild type Wzy O-antigen polymerase of SEQ ID NO: 1, which modified Wzy O-antigen polymerases improve the yield and glycosylation pattern of the O18 bioconjugates produced by the host cells. The invention further relates to methods wherein the host cells are used to produce a bioconjugate of an E. coli O18 antigen polysaccharide conjugated to a carrier protein, compositions comprising these bioconjugates, including multivalent compositions comprising bioconjugates of additional O antigen polysaccharide-serotypes.

The invention provides human AML-specific binding compounds that are able to bind a cell surface component of AML cells. Therapeutic uses of binding compounds against AML are also provided.

A method of screening is provided. In certain embodiments, the method involves a) obtaining the nucleotide sequences of: i. a heavy chain-encoding nucleic acid that encodes the variable domain of a heavy chain of a first antibody of an animal; and ii. a light chain-encoding nucleic acid that encodes the variable domain of a light chain of the first antibody; b) obtaining nucleotide sequences of cDNAs encoding at least a portion of the antibody repertoire of the animal; c) computationally screening the sequences obtained in b) to identify heavy and light chain sequences that are related by lineage to the heavy and light chain sequences of a); and d) testing at least one pair of the heavy and light chain sequences identified in c) to identify a second antibody that binds to the same antigen as the first antibody.

The present invention provides a method for manipulating the fucosylated glycan content on a recombinant protein.

Disclosed are components and systems for cell-free glycoprotein synthesis (CFGpS). In particular, the components and systems include and utilize prokaryotic cell lysates from engineered prokaryotic cell strains that have been engineered to enable cell-free synthesis of glycoproteins.

Described are compositions comprising α-galactosidase A enzymes with unique carbohydrate profiles, as well as methods for manufacturing and purifying such enzymes. Also described methods of treating, preventing, and/or ameliorating Fabry Disease by administering such enzymes to a subject in need thereof. Also described are compositions comprising migalastat in combination with such α-galactosidase A enzymes.

The present application relates to recombinant prokaryotic host cells expressing one or more 4-epimerases, one or more glycosyl-1-phosphate transferases, one or more O-oligosaccharyltransferases, and, optionally, one or more ß1,3-galactosyltransferase enzymes capable of transferring galactose to undecaprenyl pyrophosphate-linked N-Acetylgalactosamine. Also disclosed are methods for producing an O-glycosylated protein.

The present disclosure provides activated formylglycine-generating enzymes (FGE), methods of producing activated FGE, and their use in methods of producing a protein comprising a formylglycine (FGly) residue. The methods of producing activated FGE, as well as methods of use of activated FGE in producing FGly-containing proteins, include both cell-based and cell-free methods. Compositions and kits that find use, e.g., in practicing the methods of the present disclosure are also provided.