Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb 17;3(2):83-89.
doi: 10.1016/j.synbio.2018.02.002. eCollection 2018 Jun.

Cell-free synthetic biology for in vitro biosynthesis of pharmaceutical natural products

Jian Li  1 , Lingkai Zhang  1 , Wanqiu Liu  1
Affiliations
Review

Cell-free synthetic biology for in vitro biosynthesis of pharmaceutical natural products

Jian Li et al. Synth Syst Biotechnol. .

Erratum in

  • Erratum regarding previously published articles.
    [No authors listed] [No authors listed] Synth Syst Biotechnol. 2020 Oct 14;5(4):330-331. doi: 10.1016/j.synbio.2020.10.001. eCollection 2020 Dec. Synth Syst Biotechnol. 2020. PMID: 33102827 Free PMC article.

Abstract

Natural products with significant biological activities continuously act as rich sources for drug discovery and development. To harness the potential of these valuable compounds, robust methods need to be developed for their rapid and sustainable production. Cell-free biosynthesis of pharmaceutical natural products by in vitro reconstruction of the entire biosynthetic pathways represents one such solution. In this review, we focus on in vitro biosynthesis of two important classes of natural products, polyketides (PKs) and nonribosomal peptides (NRPs). First, we summarize purified enzyme-based systems for the biosynthesis of PKs, NRPs, and PK/NRP hybrids. Then, we introduce the cell-free protein synthesis (CFPS)-based technology for natural product production. With that, we discuss challenges and opportunities of cell-free synthetic biology for in vitro biosynthesis of natural products.

Keywords: Cell-free protein synthesis; Cell-free synthetic biology; In vitro biosynthesis; Natural products; Nonribosomal peptides; Polyketides; Purified enzymes.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
In vitro biosynthesis of pharmaceutical natural products with purified enzyme-based system and cell-free protein synthesis (CFPS)-based system.
Fig. 2
Fig. 2
Representative biosynthetic pathways: (A) PK: 6-deoxyerythronolide B (6-dEB), (B) NRP: gramicidin S, and (C) PK/NRP hybrid: yersiniabactin. Catalytic domains: AT, acyltransferase; KS, ketosynthase; KR, ketoreductase; DH, dehydratase; ER, enoylreductase; TE, thioesterase; A, adenylation; C, condensation; T, thiolation; E, epimerase; MT, methyltransferase; Re, reductase.
See this image and copyright information in PMC

References

    1. Katz L., Baltz R.H. Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol. 2016;43:155–176. - PubMed
    1. Newman D.J., Cragg G.M. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;9:629–661. - PubMed
    1. Fischbach M.A., Walsh C.T. Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem Rev. 2006;106:3468–3496. - PubMed
    1. Felnagle E.A., Jackson E.E., Chan Y.A., Podevels A.M., Berti A.D., McMahon M.D., Thomas M.G. Nonribosomal peptide synthetases involved in the production of medically relevant natural products. Mol Pharm. 2008;5:191–211. - PMC - PubMed
    1. Zhang H., Boghigian B.A., Armando J., Pfeifer B.A. Methods and options for the heterologous production of complex natural products. Nat Prod Rep. 2011;28:125–151. - PMC - PubMed

LinkOut - more resources