Dsm IP Assets B.v.

Marcus Hans

Jan Metske Van Der Laan

Paul Klaassen

Roelof Ary Lans Bovenberg

Martina Beishuizen

Robertus Antonius Mijndert Van Der Hoeven

Dick Schipper

Noel Nicolaas Maria Elisabeth Van Peij

Olaf Leonardus Schouten

Rémon Boer

Van Noël Nicolaas Maria Elisabeth Peij

Van Der Robertus Antonius Mijndert Hoeven

The present invention relates to a method for the production of a compound of interest by microbial fermentation, wherein the microbial host cell used has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The present invention further relates to a microbial host cell that has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The invention further relates to a compound of interest.

Recombinant host cell with deficiency in non-ribosomal peptide synthase production

The present invention describes a process for the production of an N-&#x3b1;-amino-hydroxyphenylacetyl or an N-&#x3b1;-aminophenylacetyl &#x3b2;-lactam antibiotic comprising an IPNS-catalysed conversion of a precursor tripeptide hydroxyphenylglycyl-cysteinyl-valine (HpgCV) or phenylglycyl-cysteinyl-valine (PgCV), respectively, to the N-hydroxyphenylglycyl or the N-phenylglycyl &#x3b2;-lactam antibiotic, respectively. The tripeptide HpgCV or the tripeptide PgCV may further be prepared by contacting the amino acids hydroxyphenylglycine (Hpg) or phenylglycine (Pg), cystein (C) and valine (V) with a non-ribosomal peptide synthetase (NRPS) to effect formation of the tripeptide HpgCV or the tripeptide PgCV, the NRPS comprising a first module M1 specific for Hpg or Pg, a second module M2 specific for C and a third module M3 specific for V An IPNS is further provided having an improved activity in this conversion, as well as an NRPS catalysing the formation of the tripeptides. Also a host cell is provided capable of fermentatively producing &#x3b2;-lactam antibiotics with N-&#x3b1;-amino-hydroxyphenylacetyl or an N-&#x3b1;-aminophenylacetyl side chains.

Production of &#x3b2;-Lactam antibiotics

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Den Haag, Netherlands

Marcus Hans