The disclosed HTP genomic engineering platform is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. The present disclosure provides a high-throughput (HTP) microbial genomic engineering platform that does not suffer from the myriad of problems associated with traditional microbial strain improvement programs.įurther, the HTP platform taught herein is able to rehabilitate industrial microbes that have accumulated non-beneficial mutations through decades of random mutagenesis-based strain improvement programs. Thus, there is a great need in the art for new methods of engineering industrial microbes, which do not suffer from the aforementioned drawbacks inherent with traditional strain improvement programs and greatly accelerate the process of discovering and consolidating beneficial mutations.įurther, there is an urgent need for a method by which to “rehabilitate” industrial strains that have been developed by the antiquated and deleterious processes currently employed in the field of microbial strain improvement. The accumulation of mutations in industrial strains subjected to these types of programs can become significant and may lead to an eventual stagnation in the rate of performance improvement. Not only are traditional microbial strain improvement programs inefficient, but the process can also lead to industrial strains with a high degree of detrimental mutagenic load. The process, by its very nature, is haphazard and relies upon one stumbling upon a mutation that has a desirable outcome on product output. The subsequent “improved” strain is then utilized in commercial production.Īs alluded to above, identification of improved industrial microbial strains through mutagenesis is time consuming and inefficient.
This mutagenesis process is extensively repeated until a strain demonstrates a suitable increase in product performance.
For example, many pharmaceutical and chemical industries rely on microbial strain improvement programs in which the parent strains of a microbial culture are continuously mutated through exposure to chemicals or UV radiation and are subsequently screened for performance increases, such as in productivity, yield and titer. Given the large number of products produced by modern industrial microbes, it comes as no surprise that engineers are under tremendous pressure to improve the speed and efficiency by which a given microorganism is able to produce a target product.Ī variety of approaches have been used to improve the economy of biologically-based industrial processes by “improving” the microorganism involved. Indeed, microbial cellular cultures are now used to produce products ranging from small molecules, antibiotics, vaccines, insecticides, enzymes, fuels, and industrial chemicals. The advent of genetic engineering technology has enabled scientists to design and program novel biosynthetic pathways into a variety of organisms to produce a broad range of industrial, medical, and consumer products. These products are still in large demand today and have also been accompanied by an ever increasing repertoire of products producible by microbes. Humans have been harnessing the power of microbial cellular biosynthetic pathways for millennia to produce products of interest, the oldest examples of which include alcohol, vinegar, cheese, and yogurt. 23, 2018, and is being submitted electronically via EFS-Web. The text file is 5 KB, was created on Feb. The name of the text file containing the Sequence Listing is ZYMR_001_02US_SeqList_ST25.txt. The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. The present disclosure is directed to high-throughput (HTP) microbial genomic engineering. 29, 2016, each of which are hereby incorporated by reference in their entirety, including all descriptions, references, figures, and claims for all purposes.
7, 2016, which claims the benefit of priority to U.S. § 111, claiming the benefit of priority to International Application No. 9,988,624, which is itself a Continuation of U.S. 10,336,998, which is itself a Continuation of U.S. 10,647,980, which is itself a Continuation of U.S. 10,745,694, which is itself a Continuation of U.S. 10,883,101, which is itself a Continuation of U.S.
This application is a Continuation of U.S.
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