Synthetic biopolymer

Synthetic biopolymers are human-made copies of biopolymers obtained by abiotic chemical routes.[1] Synthetic biopolymer of different chemical nature have been obtained, including polysaccharides,[2] glycoproteins,[3] peptides and proteins,[4][5] polyhydroxoalkanoates,[6] polyisoprenes.[7]

IUPAC definitions

Synthetic biopolymers: human-made copies of biopolymers obtained by abiotic chemical routes. Artificial polymer: human-made polymer that is not a biopolymer

Synthesis of biopolymer

The high molecular weight of biopolymers make their synthesis inherently laborious. Further challenges can arise from specific spatial arrangement adopted by the natural biopolymer, which may be vital for its properties/activity but not easily reproducible in the synthetic copy. Despite this, chemical approaches to obtain biopolymer are highly desirable to overcome issues arising from low abundance of the target biopolymer in Nature, the need for cumbersome isolation processes or high batch-to-batch variability or inhomogeneity of the naturally-sourced species.[8]

Examples of synthetic biopolymers obtained by chemical routes

• cis-1,4-polyisoprene[9] (synthetic analogue of rubber) and trans-1,4-polyisoprene[10] (synthetic analogue of gutta percha) are obtained by coordination polymerisation using suitable Ziegler-Natta catalysts.
• Polyhydroxoalkanoates such as poly(3-hydroxobutyrate), poly(hydroxovaleric acid) etc. obtained by polycondensation and polyaddition. Low-molecular weight polylactide and other polyglycolides can also be obtained by chemical synthesis.[11]
• Oligonucleotides and polynucleotides (DNA or RNA) can be obtain by chemical synthesis through a variety of established approaches.[12]
• A variety of proteins have been obtained by chemical synthesis. A successful approach relies on native chemical ligation, which achieves the synthesis of proteins by linking shorter unprotected peptides. This strategy allowed to obtain, amongst many others, proteins such as insulin-like growth factor 1,[13] the precursor of Aequorea green fluorescent protein[14] and the influenza A virus M2 membrane protein.[15]

Examples of biopolymers obtained by chemoenzymatic routes

• Polyhydroxoalkanoates and polyesters obtained by enzyme-assisted esterification using lipases.[6]
• Heparin,[16] heparan sulfate[17] and other glycosaminoglycans[18] and plant glycans.[19]
• Polysaccharides such as cellulose, amylose, chitin and derivatives[2]
• Natural and non-natural polynucleotides can be successfully obtained by enzyme-assisted synthesis using ligase- or polymerase-based approaches and template-assisted polymerisation.[20]

Human-made biopolymers obtained through approaches that involve genetic engineering or recombinant DNA technology are different from synthetic biopolymers and should be referred to as artificial biopolymer (e.g., artificial protein, artificial polynucleotide, etc.).[1]

Applications of synthetic biopolymers

As their natural analogues, synthetic biopolymers find applications in numerous fields, including materials for commodities, drug delivery, tissue engineering, therapeutic and diagnostic applications.

References

1. Vert, Michel; Doi, Yoshiharu; Hellwich, Karl-Heinz; Hess, Michael; Hodge, Philip; Kubisa, Przemyslaw; Rinaudo, Marguerite; Schué, François (11 January 2012). "Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)". Pure and Applied Chemistry. 84 (2): 377–410. doi:10.1351/PAC-REC-10-12-04.
2. Kadokawa, Jun-ichi (2011-07-13). "Precision Polysaccharide Synthesis Catalyzed by Enzymes". Chemical Reviews. 111 (7): 4308–4345. doi:10.1021/cr100285v. ISSN 0009-2665.
3. Hanson, Sarah; Best, Michael; Bryan, Marian C.; Wong, Chi-Huey (2004-12-01). "Chemoenzymatic synthesis of oligosaccharides and glycoproteins". Trends in Biochemical Sciences. 29 (12): 656–663. doi:10.1016/j.tibs.2004.10.004. ISSN 0968-0004. PMID 15544952.
4. Nilsson, Bradley L.; Soellner, Matthew B.; Raines, Ronald T. (3 May 2005). "Chemical Synthesis of Proteins". Annual Review of Biophysics and Biomolecular Structure. 34 (1): 91–118. doi:10.1146/annurev.biophys.34.040204.144700. ISSN 1056-8700. PMC 2845543. PMID 15869385.
5. Kent, Stephen B. H. (26 January 2009). "Total chemical synthesis of proteins". Chemical Society Reviews. 38 (2): 338–351. doi:10.1039/B700141J. ISSN 1460-4744. PMID 19169452.
6. Gross, Richard A.; Ganesh, Manoj; Lu, Wenhua (2010-08-01). "Enzyme-catalysis breathes new life into polyester condensation polymerizations". Trends in Biotechnology. 28 (8): 435–443. doi:10.1016/j.tibtech.2010.05.004. ISSN 0167-7799. PMID 20598389.
7. Natta, G. (1 January 1967). "Crystalline Synthetic High Polymers with a Sterically Regular Structure". Stereoregular Polymers and Stereospecific Polymerizations. Pergamon: 701–707. doi:10.1016/B978-1-4831-9882-8.50055-5. ISBN 9781483198828.
8. Kubicek, Christian P. (2016), "Synthetic Biopolymers", in Glieder, Anton; Kubicek, Christian P.; Mattanovich, Diethard; Wiltschi, Birgit (eds.), Synthetic Biology, Springer International Publishing, pp. 307–335, doi:10.1007/978-3-319-22708-5_9, ISBN 9783319227085
9. Rudin, Alfred; Choi, Phillip (2013-01-01), Rudin, Alfred; Choi, Phillip (eds.), "Chapter 11 - Ionic and Coordinated Polymerizations", The Elements of Polymer Science & Engineering (Third Edition), Academic Press, pp. 449–493, doi:10.1016/B978-0-12-382178-2.00011-0, ISBN 9780123821782
10. Song, Jing-She; Huang, Bao-Chen; Yu, Ding-Sheng (2001). "Progress of synthesis and application of trans-1,4-polyisoprene". Journal of Applied Polymer Science. 82 (1): 81–89. doi:10.1002/app.1826. ISSN 1097-4628.
11. Poly(lactic acid) : synthesis, structures, properties, processing and applications. Hoboken, N.J.: Wiley. 2013. ISBN 9781118088135. OCLC 898985627.
12. Reese, Colin B. (2005-10-20). "Oligo- and poly-nucleotides: 50 years of chemical synthesis". Organic & Biomolecular Chemistry. 3 (21): 3851–3868. doi:10.1039/B510458K. ISSN 1477-0539. PMID 16312051.
13. Sohma, Youhei; Pentelute, Brad L.; Whittaker, Jonathan; Hua, Qin-xin; Whittaker, Linda J.; Weiss, Michael A.; Kent, Stephen B. H. (2008). "Comparative Properties of Insulin-like Growth Factor 1 (IGF-1) and [Gly7D-Ala]IGF-1 Prepared by Total Chemical Synthesis". Angewandte Chemie International Edition. 47 (6): 1102–1106. doi:10.1002/anie.200703521. ISSN 1521-3773. PMID 18161716.
14. Sakakibara, Shumpei; Tsuji, Frederick I.; Kimura, Terutoshi; Bódi, József; Nishio, Hideki; Inui, Tatsuya; Nishiuchi, Yuji (1998-11-10). "Chemical synthesis of the precursor molecule of the Aequorea green fluorescent protein, subsequent folding, and development of fluorescence". Proceedings of the National Academy of Sciences. 95 (23): 13549–13554. Bibcode:1998PNAS...9513549N. doi:10.1073/pnas.95.23.13549. ISSN 0027-8424. PMC 24856. PMID 9811837.
15. Kochendoerfer, Gerd G.; Salom, David; Lear, James D.; Wilk-Orescan, Rosemarie; Kent, Stephen B. H.; DeGrado, William F. (1999-09-01). "Total Chemical Synthesis of the Integral Membrane Protein Influenza A Virus M2: Role of Its C-Terminal Domain in Tetramer Assembly". Biochemistry. 38 (37): 11905–11913. doi:10.1021/bi990720m. ISSN 0006-2960. PMID 10508393.
16. Linhardt, Robert J; Liu, Jian (April 2012). "Synthetic heparin". Current Opinion in Pharmacology. 12 (2): 217–219. doi:10.1016/j.coph.2011.12.002. PMC 3496756. PMID 22325855.
17. Peterson, Sherket; Frick, Amber; Liu, Jian (2009). "Design of biologically active heparan sulfate and heparin using an enzyme-based approach". Natural Product Reports. 26 (5): 610–27. doi:10.1039/B803795G. PMID 19387498.
18. Mende, Marco; Bednarek, Christin; Wawryszyn, Mirella; Sauter, Paul; Biskup, Moritz B.; Schepers, Ute; Bräse, Stefan (13 July 2016). "Chemical Synthesis of Glycosaminoglycans". Chemical Reviews. 116 (14): 8193–8255. doi:10.1021/acs.chemrev.6b00010. PMID 27410264.
19. Pfrengle, Fabian (October 2017). "Synthetic plant glycans". Current Opinion in Chemical Biology. 40: 145–151. doi:10.1016/j.cbpa.2017.09.010. PMID 29024888.
20. Kong, Dehui; Yeung, Wayland; Hili, Ryan (2016-07-11). "Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates". ACS Combinatorial Science. 18 (7): 355–370. doi:10.1021/acscombsci.6b00059. ISSN 2156-8952. PMID 27275512.