Biocatalytics, Inc.

Peter Bui

J David Rozzell, Jr

Ling Hua

A synthetic nucleic acid sequence is disclosed, comprising a non-naturally occurring polymer of nucleic acids, having a biological function encoded by the sequence and known from a starting nucleic acid sequence, and having a difference in sequence of at least about 5% between the nucleic acids of the synthetic sequence and the starting sequence. The difference between the nucleic acid sequences results in a different free energy of folding for the synthetic sequence as compared to the starting sequence, such that the synthetic sequence would be expressed better in a selected heterologous host cell than the starting sequence would be if expressed in the same heterologous host cell.

Synthetic genes for enhanced expression

A method of making a synthetic nucleic acid sequence comprises providing a starting nucleic acid sequence, which optionally encodes an amino acid sequence, and determining the predicted &Dgr;G of the sequence. The starting nucleic acid sequence can be a naturally occurring sequence or a non-naturally occurring sequence. The starting nucleic acid sequence is modified by replacing at least one codon from the starting nucleic acid sequence with a different corresponding codon to provide a modified nucleic acid sequence. As used herein, a &ldquo;different corresponding codon&rdquo; refers to a codon which does not have the identical nucleotide sequence, but which encodes the identical amino acid. The predicted &Dgr;G of the modified nucleic acid sequence is determined and compared with the &Dgr;G of the starting nucleic acid sequence. In accordance with the invention, the predicted &Dgr;G of the starting nucleic acid sequence can be determined before or after the modified starting nucleic acid is provided.

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El Monte, CA, United States of America

Peter Bui