期刊
ACS CATALYSIS
卷 6, 期 9, 页码 5935-5945出版社
AMER CHEMICAL SOC
DOI: 10.1021/acscatal.6b01559
关键词
polyketide synthase; monooxygenase; natural products; biosynthesis; catalysis
资金
- NIH [1R01GM085128, 1DP1GM106413]
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity often stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for natural product biosynthesis. Fungal polyketide synthases (PKS) are megasynthases that produce the carbon scaffold for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively catalyzing multiple similar reactions on different sites of the substrate. This Perspective will analyze several examples of fungal polyketides that are assembled from a scaffold-building iterative PKS and an accompanying, complexity-generating iterative tailoring oxygenase. In these examples, the PKS product is designed for downstream iterative oxygenations to elegantly generate additional complexity. Together, these iterative enzymes efficiently orchestrate the biosynthesis of elaborate natural products such as lovastatin, chaetoglobosin A, cytochalasin E, and aurovertin E.
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