New isolated DNA sequences, used for increasing production of the anticholesterol agent lovastatin, encode proteins involved in lovastatin biosynthesis in Monascus

摘要

Isolated DNA molecules (a) have any of the sequences (all reproduced) (1; 226 nucleotides (nt)), a lovastatin probe; (2; 9818 nt), mkA; (3; 8081 nt), mkB; (4; 1717 nt), mkC; (5; 792 nt), mkD; (6; 1228 nt), mkE; (7; 1425 nt), mkF; (8; 3356 nt), mkG; (9; 1464 nt), mkH; or (10; 2148 nt), mkI; or (b) are sequences that hybridize to (a) under stringent conditions. Independent claims are also included for the following: (1) shuttle vector containing the new molecules; (2) isolated DNA sequences (all reproduced) that are the cDNAs corresponding to genomic sequences (2)-(10); (3) shuttle vectors that contain the cDNA of (2); (4) cells transformed with at least one sequence (2)-(10) or the new cDNA; (5) method for increasing production of lovastatin (I) by transforming a (I)-producing cell with at least one of (2)-(10) or the corresponding cDNA; (6) method for producing an inhibitor (X) of HMG-CoA reductase by culturing an (X)-producing cell that has been transformed with any of (2), (3), (6) and (7), or the corresponding cDNA; (7) isolated DNA that (i) encodes the proteins (all sequences reproduced) (11; 3075 amino acids (aa)); (12; 2547 aa); (13; 524 aa); (14; 263 aa); (15; 360 aa); (16; 413 aa); (28; 1052 aa); (17; 455 aa); or (18; 543 aa) or (ii) can hybridize to (i) under stringent conditions; and (8) expression vector that contains the DNA of (7). ACTIVITY : Hypotensive; Antidiabetic; Antilipemic; Antifungal. No details of tests for these activities are given. MECHANISM OF ACTION : HMG-Co reductase Inhibitor.