公开(公告)号：WO2022018258A1

公开(公告)日：2022-01-27

申请号：PCT/EP2021/070660

申请日：2021-07-23

Applicant: SANDOZ AG

Inventor： MRAK, Peter ,  OSLAJ, Matej ,  KOPITAR, Gregor

IPC: C12P17/18 ,  C12N15/52 ,  C12N15/76

Abstract: The present invention relates to a process for the preparation of the β-lactamase inhibitor clavulanic acid by using a microorganism, comprising a step of targeted modifying said microorganism. The present invention is further directed to a process for preparing clavulanic acid by using a microorganism being capable of producing clavulanic acid, but at the same time exhibits reduced or no production of teleocidin A and/or congeners originating from the teleocidin biosynthetic pathway; to a process for preparing clavulanic acid by using a microorganism being capable of producing clavulanic acid, with this process comprising a step of testing said microorganism as to whether it is capable of producing clavulanic acid, but at the same time exhibits reduced or no production of teleocidin A, and/or other congeners originating from the teleocidin biosynthetic pathway; and to a method of testing the suitability of a strain of S. clavuligerus for being used in the production of clavulanic acid, this method comprising a step of assessing whether said strain produces teleocidin A and/or other congeners originating from the teleocidin biosynthetic pathway. The present invention further relates to a method of testing whether a culture broth that is used for culturing S. clavuligerus and producing clavulanic acid has low toxicity, comprising a step of detecting the presence or absence of teleocidin A in said culture broth. Finally, the present invention relates to S. clavuligerus that produces clavulanic acid but reduced or no teleocidin A and/or other congeners originating from the teleocidin biosynthetic pathway.