Automated system for HTP genomic engineering

An automated system for evolving a host cell to acquire a desired phenotype, the system comprising:

• i) a memory;
• and
• ii) a processor in communication with the memory, the processor configured to:
• a. define an initial promoter swap host cell library as a result of engineering the genomes of a plurality of base host cells, wherein each host cell in the initial promoter swap host cell library comprises a genetic variation comprising one or more promoters from a promoter ladder operably linked to a target gene endogenous to the host cell, wherein said promoter ladder comprises a plurality of promoters exhibiting different expression profiles in the base host cell and wherein the initial promoter swap host cell library comprises at least two different promoters from the promoter ladder;
• b. identify, based on screening and selecting individual host cells of the initial promoter swap host cell library for the desired phenotype, genetic variations that confer the desired phenotype;
• c. define a subsequent host cell library, wherein each host cell in the subsequent host cell library comprises a combination of genetic variations from at least two individual host cells from the host cell library of a preceding step;
• wherein the subsequent host cell library comprises at least one host cell with the desired phenotype;
• d. identify, based on screening and selecting individual host cells of the subsequent host cell library of the preceding step for the desired phenotype, combinations of genetic variations that confer the desired phenotype;
• and
• e. repeat steps c)-d) one or more times, in a linear or non-linear fashion, until a resultant host cell is identified as having acquired a desired level of the desired phenotype,
• wherein the resultant host cell identified in step (e) exhibits at least a 10% level increase in a measured phenotypic variable compared to that of the base host cell.