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Science 21 May 1999:
Vol. 284. no. 5418, pp. 1368 - 1372
DOI: 10.1126/science.284.5418.1368
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Reports

Modulation of Polyketide Synthase Activity by Accessory Proteins During Lovastatin Biosynthesis

Jonathan Kennedy, 1 Karine Auclair, 3 Steven G. Kendrew, 1* Cheonseok Park, 1 John C. Vederas, 3dagger C. Richard Hutchinson 12dagger

Polyketides, the ubiquitous products of secondary metabolism in microorganisms, are made by a process resembling fatty acid biosynthesis that allows the suppression of reduction or dehydration reactions at specific biosynthetic steps, giving rise to a wide range of often medically useful products. The lovastatin biosynthesis cluster contains two type I polyketide synthase genes. Synthesis of the main nonaketide-derived skeleton was found to require the previously known iterative lovastatin nonaketide synthase (LNKS), plus at least one additional protein (LovC) that interacts with LNKS and is necessary for the correct processing of the growing polyketide chain and production of dihydromonacolin L. The noniterative lovastatin diketide synthase (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts closely with an additional transesterase (LovD) responsible for assembling lovastatin from this polyketide and monacolin J.

1 School of Pharmacy,
2 Bacteriology Department, University of Wisconsin, Madison, WI 53706, USA.
3 Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
*   Present address: Dipartimento di Scienze Biochimiche, University "La Sapienza," Rome, Italy.

dagger    To whom correspondence should be addressed. E-mail: crhutchi{at}facstaff.wisc.edu (C.R.H.); john.vederas{at}ualberta.ca (J.C.V.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)