US 11,810,650 B2
Rational design of microbial-based biotherapeutics
Daniel van der Lelie, Chapel Hill, NC (US); and Safiyh Taghavi, Chapel Hill, NC (US)
Assigned to Gusto Global, LLC, Charlotte, NC (US)
Filed by Gusto Global, LLC, Charlotte, NC (US)
Filed on Oct. 3, 2019, as Appl. No. 16/592,070.
Application 16/592,070 is a continuation of application No. PCT/US2018/025805, filed on Apr. 3, 2018.
Claims priority of provisional application 62/620,752, filed on Jan. 23, 2018.
Claims priority of provisional application 62/545,733, filed on Aug. 15, 2017.
Claims priority of provisional application 62/481,062, filed on Apr. 3, 2017.
Prior Publication US 2020/0027524 A1, Jan. 23, 2020
Int. Cl. G06G 7/48 (2006.01); G16B 5/00 (2019.01); A61K 35/741 (2015.01); A61K 35/742 (2015.01); G16B 35/20 (2019.01); G16B 35/00 (2019.01); G16B 99/00 (2019.01)
CPC G16B 5/00 (2019.02) [A61K 35/741 (2013.01); A61K 35/742 (2013.01); G16B 35/00 (2019.02); G16B 35/20 (2019.02); G16B 99/00 (2019.02)] 10 Claims
 
1. A method for rational design of microbial consortia for benefiting the health of an organism, the method comprising:
providing genome annotation for a plurality of microbial strains, wherein based on the genome annotation each strain in the plurality has at least one functionality in a set of functionalities comprising:
synthesis of butyrate, synthesis of propionate, synthesis of indole, deconjugation of bile salt and conversion of bile acid into secondary bile acids, synthesis of a siderophore, uptake of a heterologously produced siderophore, and synthesis of at least one bacteriocin, wherein each of the functionalities in the set of functionalities is present in the plurality of microbial strains;
creating for each strain in the plurality, based on the genome annotation, an in silico individual metabolic model and, based on the individual metabolic models, predicting an auxotrophic profile for one or a combination of essential nutrients consisting of amino acids, vitamins, or co-factors for each strain;
obtaining one or more community metabolic models for all or a subset of the plurality of strains through integration in silico of the individual metabolic models, wherein integration of the individual models comprises modeling exchange of the one or a combination of essential nutrients between the strains within each of the one or more community metabolic models;
determining, based on the community metabolic models, a metabolic interdependency between the strains;
designating members of the plurality of strains as being part of a designed microbial consortium based on all members of the designed microbial consortium having the metabolic interdependency,
wherein the metabolic interdependency requires each of the strains to have at least one auxotrophy for the one or a combination of essential nutrients and each to be dependent on at least one of the other strains in the designed microbial consortium for growth,
wherein each of the functionalities in the set of functionalities is retained and each functionality is present in more than one strain in the designed microbial consortium; and
combining ex vivo a biologically pure culture of each of the microbial strains in the designed microbial consortium, wherein the designed microbial consortium benefits the health of the organism.