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Recent advances in systems and synthetic biology approaches for developing novel cell-factories in non-conventional yeasts.
Biotechnol Adv. 2021 Mar-Apr; 47:107695.BA

Abstract

Microbial bioproduction of chemicals, proteins, and primary metabolites from cheap carbon sources is currently an advancing area in industrial research. The model yeast, Saccharomyces cerevisiae, is a well-established biorefinery host that has been used extensively for commercial manufacturing of bioethanol from myriad carbon sources. However, its Crabtree-positive nature often limits the use of this organism for the biosynthesis of commercial molecules that do not belong in the fermentative pathway. To avoid extensive strain engineering of S. cerevisiae for the production of metabolites other than ethanol, non-conventional yeasts can be selected as hosts based on their natural capacity to produce desired commodity chemicals. Non-conventional yeasts like Kluyveromyces marxianus, K. lactis, Yarrowia lipolytica, Pichia pastoris, Scheffersomyces stipitis, Hansenula polymorpha, and Rhodotorula toruloides have been considered as potential industrial eukaryotic hosts owing to their desirable phenotypes such as thermotolerance, assimilation of a wide range of carbon sources, as well as ability to secrete high titers of protein and lipid. However, the advanced metabolic engineering efforts in these organisms are still lacking due to the limited availability of systems and synthetic biology methods like in silico models, well-characterised genetic parts, and optimized genome engineering tools. This review provides an insight into the recent advances and challenges of systems and synthetic biology as well as metabolic engineering endeavours towards the commercial usage of non-conventional yeasts. Particularly, the approaches in emerging non-conventional yeasts for the production of enzymes, therapeutic proteins, lipids, and metabolites for commercial applications are extensively discussed here. Various attempts to address current limitations in designing novel cell factories have been highlighted that include the advances in the fields of genome-scale metabolic model reconstruction, flux balance analysis, 'omics'-data integration into models, genome-editing toolkit development, and rewiring of cellular metabolisms for desired chemical production. Additionally, the understanding of metabolic networks using 13C-labelling experiments as well as the utilization of metabolomics in deciphering intracellular fluxes and reactions have also been discussed here. Application of cutting-edge nuclease-based genome editing platforms like CRISPR/Cas9, and its optimization towards efficient strain engineering in non-conventional yeasts have also been described. Additionally, the impact of the advances in promising non-conventional yeasts for efficient commercial molecule synthesis has been meticulously reviewed. In the future, a cohesive approach involving systems and synthetic biology will help in widening the horizon of the use of unexplored non-conventional yeast species towards industrial biotechnology.

Authors+Show Affiliations

School of Energy Science and Engineering, Indian Institute of Technology Kharagpur, West Bengal 721302, India.School of Bioscience, Indian Institute of Technology Kharagpur, West Bengal 721302, India.School of Energy Science and Engineering, Indian Institute of Technology Kharagpur, West Bengal 721302, India.School of Energy Science and Engineering, Indian Institute of Technology Kharagpur, West Bengal 721302, India; P.K. Sinha Centre for Bioenergy and Renewables, Indian Institute of Technology Kharagpur, West Bengal 721302, India. Electronic address: amitghosh@iitkgp.ac.in.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

33465474

Citation

Patra, Pradipta, et al. "Recent Advances in Systems and Synthetic Biology Approaches for Developing Novel Cell-factories in Non-conventional Yeasts." Biotechnology Advances, vol. 47, 2021, p. 107695.
Patra P, Das M, Kundu P, et al. Recent advances in systems and synthetic biology approaches for developing novel cell-factories in non-conventional yeasts. Biotechnol Adv. 2021;47:107695.
Patra, P., Das, M., Kundu, P., & Ghosh, A. (2021). Recent advances in systems and synthetic biology approaches for developing novel cell-factories in non-conventional yeasts. Biotechnology Advances, 47, 107695. https://doi.org/10.1016/j.biotechadv.2021.107695
Patra P, et al. Recent Advances in Systems and Synthetic Biology Approaches for Developing Novel Cell-factories in Non-conventional Yeasts. Biotechnol Adv. 2021 Mar-Apr;47:107695. PubMed PMID: 33465474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recent advances in systems and synthetic biology approaches for developing novel cell-factories in non-conventional yeasts. AU - Patra,Pradipta, AU - Das,Manali, AU - Kundu,Pritam, AU - Ghosh,Amit, Y1 - 2021/01/16/ PY - 2020/09/13/received PY - 2020/12/14/revised PY - 2021/01/09/accepted PY - 2021/1/20/pubmed PY - 2021/4/27/medline PY - 2021/1/19/entrez KW - (13)C-metabolic flux analysis KW - CRISPR/Cas9 KW - Carbon rewiring KW - Cre-loxP KW - Flux balance analysis KW - Genome-scale metabolic model KW - Homologous recombination KW - Metabolic engineering SP - 107695 EP - 107695 JF - Biotechnology advances JO - Biotechnol Adv VL - 47 N2 - Microbial bioproduction of chemicals, proteins, and primary metabolites from cheap carbon sources is currently an advancing area in industrial research. The model yeast, Saccharomyces cerevisiae, is a well-established biorefinery host that has been used extensively for commercial manufacturing of bioethanol from myriad carbon sources. However, its Crabtree-positive nature often limits the use of this organism for the biosynthesis of commercial molecules that do not belong in the fermentative pathway. To avoid extensive strain engineering of S. cerevisiae for the production of metabolites other than ethanol, non-conventional yeasts can be selected as hosts based on their natural capacity to produce desired commodity chemicals. Non-conventional yeasts like Kluyveromyces marxianus, K. lactis, Yarrowia lipolytica, Pichia pastoris, Scheffersomyces stipitis, Hansenula polymorpha, and Rhodotorula toruloides have been considered as potential industrial eukaryotic hosts owing to their desirable phenotypes such as thermotolerance, assimilation of a wide range of carbon sources, as well as ability to secrete high titers of protein and lipid. However, the advanced metabolic engineering efforts in these organisms are still lacking due to the limited availability of systems and synthetic biology methods like in silico models, well-characterised genetic parts, and optimized genome engineering tools. This review provides an insight into the recent advances and challenges of systems and synthetic biology as well as metabolic engineering endeavours towards the commercial usage of non-conventional yeasts. Particularly, the approaches in emerging non-conventional yeasts for the production of enzymes, therapeutic proteins, lipids, and metabolites for commercial applications are extensively discussed here. Various attempts to address current limitations in designing novel cell factories have been highlighted that include the advances in the fields of genome-scale metabolic model reconstruction, flux balance analysis, 'omics'-data integration into models, genome-editing toolkit development, and rewiring of cellular metabolisms for desired chemical production. Additionally, the understanding of metabolic networks using 13C-labelling experiments as well as the utilization of metabolomics in deciphering intracellular fluxes and reactions have also been discussed here. Application of cutting-edge nuclease-based genome editing platforms like CRISPR/Cas9, and its optimization towards efficient strain engineering in non-conventional yeasts have also been described. Additionally, the impact of the advances in promising non-conventional yeasts for efficient commercial molecule synthesis has been meticulously reviewed. In the future, a cohesive approach involving systems and synthetic biology will help in widening the horizon of the use of unexplored non-conventional yeast species towards industrial biotechnology. SN - 1873-1899 UR - https://www.unboundmedicine.com/medline/citation/33465474/Recent_advances_in_systems_and_synthetic_biology_approaches_for_developing_novel_cell_factories_in_non_conventional_yeasts_ DB - PRIME DP - Unbound Medicine ER -