OLIVETOL SYNTHASE VARIANTS AND METHODS FOR PRODUCTION OF OLIVETOLIC ACID AND ITS ANALOG COMPOUNDS

    公开(公告)号:US20220177858A1

    公开(公告)日:2022-06-09

    申请号:US17604722

    申请日:2020-04-17

    Abstract: Described herein are non-natural olivetol synthase (OLS) variants, nucleic acids, engineered cells, method s for preparing cannabinoids, and compositions thereof. The non-natural olivetol OLS variants form desired cannabinoid precursor and products at increased rates, have higher affinity for pathway substrates, and/or byproducts are formed in lower amounts in their presence, as compared to wild type OLS. The OLS variants can be used to form linear polyketides, and can be expressed in an engineered cell having a pathway to form cannabinoids, which include CBGA, its analogs and derivatives. CBGA can be used for the preparation of cannabigerol (CBG), which can be used in therapeutic compositions.

    OLIVETOLIC ACID CYCLASE VARIANTS AND METHODS FOR THEIR USE

    公开(公告)号:US20220315969A1

    公开(公告)日:2022-10-06

    申请号:US17616842

    申请日:2020-06-05

    Abstract: Described herein are olivetolic acid cyclases (OAC) including non-natural variants capable of forming a 2,4-dihydroxy-6-alkylbenzoic acid from a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate. In some examples, the non-natural OAC is capable of forming a 2,4-dihydroxy-6-alkylbenzoic acid from a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate at a greater rate. In some examples, the non-natural OAC has a higher affinity for a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate, as compared to the wild type OAC. The non-natural OAC can be used with olivetol synthase (OLS) to form the 2,4-dihydroxy-6-alkylbenzoic acid from malonyl-CoA and acyl-CoA through to a 3,5,7-trioxoacyl-CoAintermediate. The non-natural OAC (and OLS) can be expressed in an engineered cell having a pathway to form cannabinoids, which include CBGA, its analogs and derivatives. CBGA can be used for the preparation of cannabigerol (CBG), which can be used in therapeutic compositions.

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