Abstract
Heterologous biosynthesis has been long pursued as a viable approach for high efficiency production of natural products with various industrial values. Conventional methods for heterologous biosynthesis use the mono-culture of an engineered microbe for accommodating the whole target biosynthetic pathway to produce the desired product. The emergence of modular co-culture engineering, which divides the pathway between multiple co-culture strains, presents a new perspective to conduct heterologous biosynthesis and improve the bioproduction performance of natural products. This review highlights recent advances in utilizing the modular co-culture engineering approaches to address the challenges of plant and fungal natural product biosynthesis. Potential directions for future research in this promising field are also discussed.
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References
Ahmadi MK, Pfeifer BA (2016) Recent progress in therapeutic natural product biosynthesis using Escherichia coli. Curr Opin Biotechnol 42:7–12. https://doi.org/10.1016/j.copbio.2016.02.010
Ahmadi MK, Fang L, Moscatello N, Pfeifer BA (2016) E coli metabolic engineering for gram scale production of a plant-based anti-inflammatory agent. Metab Eng 38:382–388. https://doi.org/10.1016/j.ymben.2016.10.001
Becker J, Wittmann C (2016) Systems metabolic engineering of Escherichia coli for the heterologous production of high value molecules-a veteran at new shores. Curr Opin Biotechnol 42:178–188. https://doi.org/10.1016/j.copbio.2016.05.004
Camacho-Zaragoza JM, Hernandez-Chavez G, Moreno-Avitia F, Ramirez-Iniguez R, Martinez A, Bolivar F, Gosset G (2016) Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol. Microb Cell Fact 15:163. https://doi.org/10.1186/s12934-016-0562-z
Chen Z, Sun X, Li Y, Yan Y, Yuan Q (2017) Metabolic engineering of Escherichia coli for microbial synthesis of monolignols. Metab Eng 39:102–109. https://doi.org/10.1016/j.ymben.2016.10.021
Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochem Biophys Acta 1830:3670–3695. https://doi.org/10.1016/j.bbagen.2013.02.008
Ganesan V, Li Z, Wang X, Zhang H (2017) Heterologous biosynthesis of natural product naringenin by co-culture engineering. Synth Syst Biotechnol 2:236–242. https://doi.org/10.1016/j.synbio.2017.08.003
Gupta SS (1994) Prospects and perspectives of natural products in medicine. Indian J Pharmacol 26:1–12
Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24:393–416. https://doi.org/10.1039/b603084j
Jones JA, Wang X (2017) Use of bacterial co-cultures for the efficient production of chemicals. Curr Opin Biotechnol 53:33–38. https://doi.org/10.1016/j.copbio.2017.11.012
Jones JA et al (2016) Experimental and computational optimization of an Escherichia coli co-culture for the efficient production of flavonoids. Metab Eng 35:55–63. https://doi.org/10.1016/j.ymben.2016.01.006
Jones JA et al (2017) Complete biosynthesis of anthocyanins using E. coli polycultures. MBio. https://doi.org/10.1128/mbio.00621-17
Kovacic P, Somanathan R (2010) Multifaceted approach to resveratrol bioactivity: focus on antioxidant action, cell signaling and safety. Oxid Med Cell Long 3:86–100. https://doi.org/10.4161/oxim.3.2.3
Lee K-H (2004) Current developments in the discovery and design of new drug candidates from plant natural product leads. J Nat Prod 67:273–283. https://doi.org/10.1021/np030373o
Li S, Li Y, Smolke CD (2018a) Strategies for microbial synthesis of high-value phytochemicals. Nat Chem 10:395–404. https://doi.org/10.1038/s41557-018-0013-z
Li T, Zhou W, Bi H, Zhuang Y, Zhang T, Liu T (2018b) Production of caffeoylmalic acid from glucose in engineered Escherichia coli. Biotechnol Lett 40:1057–1065. https://doi.org/10.1007/s10529-018-2580-x
Liu X et al (2018a) Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides. Metab Eng 47:243–253. https://doi.org/10.1016/j.ymben.2018.03.016
Liu Y et al (2018b) Engineered monoculture and co-culture of methylotrophic yeast for de novo production of monacolin J and lovastatin from methanol. Metab Eng 45:189–199. https://doi.org/10.1016/j.ymben.2017.12.009
Luo Y et al (2015) Engineered biosynthesis of natural products in heterologous hosts. Chem Soc Rev 44:5265–5290. https://doi.org/10.1039/c5cs00025d
Marmann A, Aly AH, Lin W, Wang B, Proksch P (2014) Co-cultivation: a powerful emerging tool for enhancing the chemical diversity of microorganisms. Mar Drugs 12:1043–1065. https://doi.org/10.3390/md12021043
Niu FX, He X, Wu YQ, Liu JZ (2018) Enhancing production of pinene in Escherichia coli by using a combination of tolerance, evolution, and modular co-culture engineering. Front Microbiol 9:1623. https://doi.org/10.3389/fmicb.2018.01623
Schueffler A, Anke T (2014) Fungal natural products in research and development. Nat Prod Rep 31:1425–1448. https://doi.org/10.1039/c4np00060a
Sgobba E et al (2018) Synthetic Escherichia coli-Corynebacterium glutamicum consortia for l-lysine production from starch and sucrose. Bioresour Technol 260:302–310. https://doi.org/10.1016/j.biortech.2018.03.113
Thuan NH, Chaudhary AK, Van Cuong D, Cuong NX (2018a) Engineering co-culture system for production of apigetrin in Escherichia coli. J Ind Microbiol Biotechnol 45:175–185. https://doi.org/10.1007/s10295-018-2012-x
Thuan NH, Trung NT, Cuong NX, Van Cuong D, Van Quyen D, Malla S (2018b) Escherichia coli modular coculture system for resveratrol glucosides production. World J Microbiol Biotechnol 34:75. https://doi.org/10.1007/s11274-018-2458-z
Wang J et al (2018) A novel process for cadaverine bio-production using a consortium of two engineered Escherichia coli. Front Microbiol 9:1312. https://doi.org/10.3389/fmicb.2018.01312
Zhang H, Wang X (2016) Modular co-culture engineering, a new approach for metabolic engineering. Metab Eng 37:114–121. https://doi.org/10.1016/j.ymben.2016.05.007
Zhang H, Wang Y, Pfeifer BA (2008) Bacterial hosts for natural product production. Mol Pharm 5:212–225. https://doi.org/10.1021/mp7001329
Zhang H, Boghigian BA, Armando J, Pfeifer BA (2011) Methods and options for the heterologous production of complex natural products. Nat Prod Rep 28:125–151. https://doi.org/10.1039/c0np00037j
Zhang H, Pereira B, Li Z, Stephanopoulos G (2015) Engineering Escherichia coli coculture systems for the production of biochemical products. Proc Natl Acad Sci USA 112:8266–8271. https://doi.org/10.1073/pnas.1506781112
Zhang S, Wang S, Zhan J (2016) Engineered biosynthesis of medicinally important plant natural products in microorganisms. Curr Top Med Chem 16:1740–1754
Zhang W et al (2017) Production of naringenin from d-xylose with co-culture of E. coli and S. cerevisiae. Eng Life Sci 17:1021–1029. https://doi.org/10.1002/elsc.201700039
Zhou K, Qiao K, Edgar S, Stephanopoulos G (2015) Distributing a metabolic pathway among a microbial consortium enhances production of natural products. Nat Biotechnol 33:377. https://doi.org/10.1038/nbt.3095
Acknowledgements
This work is supported by startup research funds provided by Rutgers, The State University of New Jersey. Tingting Chen is a recipient of CSC PhD fellowship.
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Chen, T., Zhou, Y., Lu, Y. et al. Advances in heterologous biosynthesis of plant and fungal natural products by modular co-culture engineering. Biotechnol Lett 41, 27–34 (2019). https://doi.org/10.1007/s10529-018-2619-z
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DOI: https://doi.org/10.1007/s10529-018-2619-z