Merck + Co., Inc.

University of Virginia Patent Foundation

Victor A Vinci

Michael J Conder

Christopher D Reeves

John A Rambosek

Phyllis C McAda

Charles Ray Davis

Lee E Hendrickson

Robert W Stieber

John L Gainer

Rebecca L Dabora

Giorgio Carta

William H Cover

Anil Goyal

Anderson Hong

W Scott Borneman

Timothy W Weber

Bioprocesses are disclosed for the production of compounds which can be produced from a dipeptide intermediate. The process comprises production of a recombinant polypeptide which contains the dipeptide intermediate. The dipeptide intermediate is further processed to ultimately provide the finished product.

Bioprocess for production of dipeptide based compounds

DNA encoding triol polyketide synthase (TPKS) has been isolated, purified and sequenced. Expression vectors comprising TPKS, cells transformed with the expression vectors, and processes employing the transformed cells are provided.

DNA encoding triol polyketide synthase

An immobilized lipase is employed in an organic solvent to esterify diol lactone derivatives of HMG-CoA reductase inhibitors to form HMG-CoA reductase inhibitors of formula (I). ##STR1## This process allows for the efficient, one-step production of HMG-CoA reductase inhibitors of structural formula (I).

Process for synthesis of acylated HMG-CoA reductase inhibitors from a

Novel strains of Aspergillus terreus have been discovered which provide fermentation production of at least 5.2 g/L of 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl ]-3(R),5(R)-dihydroxyheptanoic acid (triol acid, I), but with production of not more than 0.85 g/L of (triol acid)-related side products and specifically less than 0.10 mg/liter of lovastatin. The predominant fermentation product triol acid, may be converted in a straightforward manner to its lactone form, in which it is an inhibitor of HMG-CoA reductase and thus useful as an antihypercholesterolemic agent, and in which it may also serve as an intermediate for preparation of other HMG-CoA reductase inhibitors.

Mutant strains of Aspergillus terreus for producing

Growing community of inventors

Charlottesville, VA, United States of America

Victor A Vinci