Access to High Value Natural and Unnatural Products through Hyphenating Chemical Synthesis and Biosynthesis

Abstract

Access to natural products and their analogues is crucial. Such compounds have, for many years, played a central role in the area of drug discovery as well as in providing tools for chemical biology­. The ability to quickly and inexpensively acquire genome sequences has accelerated the field of natural product research. Access to genomic data coupled with new technologies for the engineering of organisms is resulting in the identification of large numbers of previously undiscovered natural products as well as an increased understanding of how the biosynthetic pathways responsible for the biogenesis of these compounds may be manipulated. This short review summarizes and reflects upon approaches to accessing natural products and has a particular focus on approaches combining molecular biology and synthetic chemistry.

1 Introduction

2 CHEM: Total Synthesis

3 BIO-CHEM: Semi-Synthesis

4 CHEM-BIO: Precursor Directed Biosynthesis

5 BIO-CHEM-BIO: Mutasynthesis

6 BIO-BIO: Combinatorial Biosynthesis

7 BIO-BIO-CHEM: Genochemetics: Gene Expression Enabling Synthetic Diversification

8 Conclusions and Future Directions in Natural Product Analogue Generation

Key words

alkyl halides - antibiotics - antifungal agents - antitumor agents - biosynthesis - chemoselectivity - cross-coupling

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