Abstract

AnE. colicell factory was constructed for production of the monomer moiety of scytonemin. Combining this biological system with chemo-synthetic dimerization will contribute to semi-synthetic scytonemin production.

Highlights

  • Alkaloids, a diverse group of nitrogen-containing natural products, are produced by a large variety of organisms including bacteria, fungi, insects, plants and animals

  • The in vitro studies on scyC only accumulated 3a,44 we found that in vivo production of a monomer moiety of scytonemin in E. coli can be achieved by expression of only three genes, scyABC, from N. punctiforme

  • The final dimerization step remains a major hurdle for the complete production of scytonemin in E. coli

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Summary

Introduction

A diverse group of nitrogen-containing natural products, are produced by a large variety of organisms including bacteria, fungi, insects, plants and animals. Numerous alkaloids are pharmacologically well characterized and are used as clinical drugs, ranging from chemotherapeutics to analgesic agents.[1] Studies on plant alkaloids suggest that they are involved in the defense mechanism against herbivores, insects and pathogens.[2] Since alkaloids are toxic, they are usually produced in small quantities by their native producer organisms. Scytonemin is an alkaloid pigment consisting of a symmetrical dimeric carbon skeleton composed of fused heterocyclic units with conjugated double-bond distribution (Fig. 1) synthesized by numerous cyanobacteria.[3] Scytonemin is the first described small molecule that inhibits human polo-like kinase 1 (PLK1).[4] PLK1 has multiple functions during mitosis and plays a significant role in maintaining the genomic stability.[5] PLK1 is highly expressed in a broad spectrum of cancer cells, indicating its possibility of being involved in carcinogenesis.[6] Scytonemin (at 3–4 μM concentration) can

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