Abstract: Methods for determining a property that affects expression of polynucleotides are provided. A plurality of polynucleotides each encoding a polypeptide sequence is constructed. A frequency that a sequence element is used in a first polynucleotide is different than in a second polynucleotide. Each polynucleotide is expressed in an expression system to obtain an expression property value thereby constructing a dataset that contains, for each respective polynucleotide, sequence element occurrence in the respective polynucleotide and the measured expression property value of the respective polynucleotide. A model is computed that describes variation in the measured expression property values as a function of a plurality of variables and weights.

Abstract: Provided are methods, compositions, and kits for molecular cloning of DNA using DNA topoisomerase. The methods comprise (I) combining into a mixture (A) a first polynucleotide, comprising an origin of replication, a selectable marker, two topoisomerase recognition sequences, and two nicking agent recognition sequences, each of the topoisomerase recognition sequences being within 50 nucleotides of at least one of the nicking agent recognition sequences and each of two nicking agent recognition sequences being nicked, with (B) a sequence-specific topoisomerase and (C) a second polynucleotide, having a 5? hydroxyl on each end; and (II) transforming the mixture into a host organism, thereby cloning the second polynucleotide. Formation or purification of a DNA-protein adduct prior to the addition of the second polynucleotide is not required. Also provided are vector sequences to facilitate performance of the methods and methods for modifying a vector of interest to render it useful in the disclosed methods.

Abstract: A substantially pure Candida host cell for the production of a ?-carboxyl-?-hydroxy fatty acid having a carbon chain length in the range from C6 to C22, a ?,?-dicarboxylic fatty acid having a carbon chain length in the range from C6 to C22, or mixtures thereof, is provided. The Candida host cell is characterized by a first genetic modification class and a second genetic modification class. The first genetic modification class comprises one or more genetic modifications that disrupt the peroxisomal ?-oxidation pathway. The second genetic modification class comprises one or more genetic modifications that collectively or individually disrupt at least one gene selected from the group consisting of a CYP52A type cytochrome P450, a fatty alcohol oxidase, and an alcohol dehydrogenase.

Abstract: A method of determining a property that affects expression of polynucleotides in an expression system. A plurality of polynucleotides, each encoding a polypeptide sequence, is constructed. An amino acid is encoded a plurality of times in both a first and second polynucleotide in the plurality. The amino acid is encodable by a plurality of synonymous codons including a first codon. The first codon is in the first polynucleotide at a first frequency relative to other synonymous codons, and is in the second polynucleotide at a second frequency relative to other synonymous codons. The first and second frequencies are different. Each polynucleotide is individually expressed in the expression system to measure an expression property value of the polynucleotides, thereby determining a property that affects expression of polynucleotides. The property is an effect that a frequency of use of one or more codons has on expression of polynucleotides in the expression system.

Abstract: Methods, computer systems, and computer program products for biopolymer engineering. A variant set for a biopolymer of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the biopolymer of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space. A variant set comprising a plurality of variants of the biopolymer of interest is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.

Abstract: Methods, computer systems, and computer program products for antibody engineering. A variant set for an antibody of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the antibody of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of position collectively define an antibody sequence space. A variant set comprising a plurality of variants of the antibody is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the antibody of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.

Abstract: Methods, computer systems, and computer program products for biopolymer engineering. A variant set for a biopolymer of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the biopolymer of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space. A variant set comprising a plurality of variants of the biopolymer of interest is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.

Abstract: Computer systems, computer program products and methods for designing oligonucleotides are provided. A set of sequence elements is defined. Each sequence element represents an amino acid sequence segment or a nucleic acid sequence segment. The set of sequence elements collectively represent a design nucleic acid sequence. The set of sequence elements are displayed as a plurality icons in a linear or a near linear arrangement such that each respective icon in the plurality of icons uniquely represents a corresponding sequence element in the set of sequence elements. In this representation, neighboring icons in the plurality of icons represent neighboring sequence elements in the set of sequence elements. Each respective icon in the plurality of icons depicts a directional property for the corresponding sequence element in the set of sequence elements. An oligonucleotide selection module is used to identify oligonucleotides in the design nucleic acid sequence.

Abstract: Methods, computer systems, and computer program products for biopolymer engineering. A variant set for a biopolymer of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the biopolymer of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space. A variant set comprising a plurality of variants of the biopolymer of interest is selected. A property of all or a portion of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.

Abstract: A method of determining a property that affects expression of polynucleotides in an expression system. A plurality of polynucleotides, each encoding a polypeptide sequence, is constructed. An amino acid is encoded a plurality of times in both a first and second polynucleotide in the plurality. The amino acid is encodable by a plurality of synonymous codons including a first codon. The first codon is in the first polynucleotide at a first frequency relative to other synonymous codons, and is in the second polynucleotide at a second frequency relative to other synonymous codons. The first and second frequencies are different. Each polynucleotide is individually expressed in the expression system to measure an expression property value of the polynucleotides, thereby determining a property that affects expression of polynucleotides. The property is an effect that a frequency of use of one or more codons has on expression of polynucleotides in the expression system.

Abstract: A method of designing a polynucleotide sequence encoding a polypeptide sequence of a predetermined polypeptide is provided. A frequency lookup table corresponding to an expression system is obtained. The table comprises a plurality of sequence elements and a plurality of frequency ranges, each frequency range for a corresponding sequence element. Each frequency range is a range of frequencies with which a corresponding sequence element can occur in a polynucleotide. The polynucleotide sequence is defined using the frequency lookup table by determining, for each respective sequence element in the frequency lookup table, whether the respective sequence element encodes a portion of the polypeptide sequence. When the respective sequence element encodes a portion of the polypeptide sequence, the sequence element is incorporated into the polynucleotide at a frequency of occurrence that is within the frequency range specified for the respective sequence element in the lookup table.

Abstract: Methods, computer systems, and computer program products for biopolymer engineering. A variant set for a biopolymer of interest is constructed by identifying, using a plurality of rules, a plurality of positions in the biopolymer of interest and, for each respective position in the plurality of positions, substitutions for the respective position. The plurality of positions and the substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space. A variant set comprising a plurality of variants of the biopolymer of interest is selected. A property of all or a position of the variants in the variant set is measured. A sequence-activity relationship is modeled between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or the portion of the variants in the variant set.