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Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids

  • Natural Products - Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

A Correction to this article was published on 12 November 2020

This article has been updated

Abstract

Isoprenoids are a large class of natural products with myriad applications as bioactive and commercial compounds. Their diverse structures are derived from the biosynthetic assembly and tailoring of their scaffolds, ultimately constructed from two C5 hemiterpene building blocks. The modular logic of these platforms can be harnessed to improve titers of valuable isoprenoids in diverse hosts and to produce new-to-nature compounds. Often, this process is facilitated by the substrate or product promiscuity of the component enzymes, which can be leveraged to produce novel isoprenoids. To complement rational enhancements and even re-programming of isoprenoid biosynthesis, high-throughput approaches that rely on searching through large enzymatic libraries are being developed. This review summarizes recent advances and strategies related to isoprenoid synthetic biology, combinatorial biosynthesis, and chemo-enzymatic synthesis, focusing on the past 5 years. Emerging applications of cell-free biosynthesis and high-throughput tools are included that culminate in a discussion of the future outlook and perspective of isoprenoid biosynthetic engineering.

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  • 12 November 2020

    Unfortunately, the article title was published incorrectly in the HTML version (online version only) of the online published article.

Abbreviations

ADH:

Alcohol-dependent hemiterpene

CoA:

Coenzyme A

CFB:

Cell-free biosynthesis

CFPS:

Cell-free protein synthesis

CRISPR:

Clustered regularly interspaced short palindromic repeats

CYP:

Cytochrome P450

DKP:

Diketopiperazine

DMAA:

Dimethylallyl alcohol

DMAPP:

Dimethylallyl pyrophosphate

DXP:

1-Deoxy-d-xylulose-5-phosphate

FPP:

Farnesyl pyrophosphate

G3P:

Glyceraldehyde-3-phosphate

GGPP:

Geranylgeranyl pyrophosphate

GPP:

Geranyl pyrophosphate

GT:

Glycosyltransferase

HMG-CoA:

3-Hydroxy-3-methyl-glutaryl-CoA

IPP:

Isopentenyl pyrophosphate

ISO:

Isoprenol

MT:

Methyltransferase

MVA:

Mevalonate

NPP:

Neryl pyrophosphate

PTase:

Prenyltransferase

SAM:

(S)-Adenosylmethionine

TC:

Terpene cyclase

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Acknowledgements

Financial support is provided by the National Institutes of Health (Award Number GM124112) and the Thomas Lord Distinguished Professorship Endowment.

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Authors and Affiliations

  1. Department of Chemistry, NC State University, Raleigh, NC, 27695, USA

    Alexandra A. Malico, Miles A. Calzini, Anuran K. Gayen & Gavin J. Williams

  2. Comparative Medicine Institute, NC State University, Raleigh, NC, 27695, USA

    Gavin J. Williams

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  1. Alexandra A. Malico
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  2. Miles A. Calzini
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  4. Gavin J. Williams
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Malico, A.A., Calzini, M.A., Gayen, A.K. et al. Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids. J Ind Microbiol Biotechnol 47, 675–702 (2020). https://doi.org/10.1007/s10295-020-02306-3

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