Exploiting marine actinomycete biosynthetic pathways for drug discovery.
Drug discovery relies on the generation of large numbers of structurally diverse compounds from which a potential candidate can be identified. To this end, actinomycetes have often been exploited because of their ability to biosynthesize an impressive array of novel metabolites particularly polyketides. The genetic organization of polyketide synthases (PKSs) makes them readily amenable to manipulation, and thus re-engineering artificial or hybrid PKSs to produce unnatural natural products is a reality. This review highlights two approaches we have used to generate novel polyketides by manipulating genes responsible for starter unit biosynthesis in the 'Streptomyces maritimus' enterocin type II PKS. Our preliminary investigation into the biosynthesis of neomarinone, a rare marine actinomycete-derived meroterpenoid, is also presented.
Moore
Bradley S
BS
College of Pharmacy, University of Arizona, Tucson, AZ 85721-027, USA. moore@pharmacy.arizona.edu
Kalaitzis
John A
JA
Xiang
Longkuan
L
D039903:Actinobacteria / Q000302:isolation & purification / Q000378:metabolism*; D015195:Drug Design; D005818:Genetic Engineering; D019015:Geologic Sediments / Q000382:microbiology; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism; D012623:Seawater / Q000382:microbiology; D013302:Streptomyces; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism
D018942:Macrolides; D011753:Pyrones; D013729:Terpenes; D048630:Polyketide Synthases