Journal
CURRENT OPINION IN CHEMICAL BIOLOGY
Volume 16, Issue 1-2, Pages 179-185Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cbpa.2011.12.016
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Science and Technology Agency, Japan
- Grants-in-Aid for Scientific Research [23241068] Funding Source: KAKEN
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The structurally and mechanistically simple type III polyketide synthases (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of polyketide scaffolds with remarkably diverse structures and biological activities. By exploiting the enzymes, we combined precursor-directed biosynthesis with nitrogen-containing substrates and structure-based enzyme engineering and generated unnatural, novel polyketide-alkaloid scaffolds with promising biological activities. The nucleophilic nitrogen atom and the engineered enzymes thus facilitated the formation of additional C-C and C-N bonds during the enzymatic transformations. The methodology will contribute to the further production of chemically and structurally divergent, unnatural natural products, as well as the rational design of novel biocatalysts with unprecedented catalytic functions.
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