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1.
Strategy for improving L-isoleucine production efficiency in Corynebacterium glutamicum.
Wang, X
Applied microbiology and biotechnology. 2019;(5):2101-2111
Abstract
As one of the three branched-chain amino acids essential for human body, L-isoleucine is widely used in food, medicine, and feed industries. At present, L-isoleucine is mainly produced by microbial fermentation, and the main production strain is Corynebacterium glutamicum. The biosynthetic pathway of L-isoleucine in C. glutamicum is complex, and the activity of key enzymes and the transcription of key genes in the pathway are strictly regulated. The intracellularly synthesized L-isoleucine is secreted by transporters, and the activity of the transporters is also regulated. These intricate regulatory mechanisms increase the difficulty to engineer the L-isoleucine-producing C. glutamicum. This article focuses on the mechanism of L-isoleucine biosynthesis, secretion, and regulation in C. glutamicum and reviews the various metabolic engineering strategies for improving L-isoleucine production efficiency in C. glutamicum.
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2.
Challenges and tackles in metabolic engineering for microbial production of carotenoids.
Wang, C, Zhao, S, Shao, X, Park, JB, Jeong, SH, Park, HJ, Kwak, WJ, Wei, G, Kim, SW
Microbial cell factories. 2019;(1):55
Abstract
Naturally occurring carotenoids have been isolated and used as colorants, antioxidants, nutrients, etc. in many fields. There is an ever-growing demand for carotenoids production. To comfort this, microbial production of carotenoids is an attractive alternative to current extraction from natural sources. This review summarizes the biosynthetic pathway of carotenoids and progresses in metabolic engineering of various microorganisms for carotenoid production. The advances in synthetic pathway and systems biology lead to many versatile engineering tools available to manipulate microorganisms. In this context, challenges and possible directions are also discussed to provide an insight of microbial engineering for improved production of carotenoids in the future.
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3.
Recent advances in engineering Corynebacterium glutamicum for utilization of hemicellulosic biomass.
Choi, JW, Jeon, EJ, Jeong, KJ
Current opinion in biotechnology. 2019;:17-24
Abstract
Corynebacterium glutamicum has been mainly used for industrial production of amino acids, and in recent years, it has also been successfully engineered to broaden its range of substrate and product profiles. In particular, C. glutamicum has been engineered to use non-natural sugar substrates (mainly pentoses) derived from hemicellulosic feedstock, which is the second abundant component of lignocellulosic biomass. Engineering of the host in this context can greatly contribute to the development of an economic and sustainable bioprocess. The present review focuses on the recent progress in engineering C. glutamicum towards efficient utilization of pentose sugars derived in hemicellulose and for direct utilization of hemicellulose. In addition, use of C. glutamicum as a biocatalyst for bioconversion of low-value sugars derived from hemicellulose to high-value product has been reviewed.
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4.
Advances in 2-phenylethanol production from engineered microorganisms.
Wang, Y, Zhang, H, Lu, X, Zong, H, Zhuge, B
Biotechnology advances. 2019;(3):403-409
Abstract
2-Phenylethanol (2-PE) is an important flavor ingredient with a rose-like odor. Due to concerns about the toxic byproducts potentially found in 2-PE from chemical synthesis, consumers prefer the natural aroma compound, promoting the biosynthesis of 2-PE. Various microorganisms produce 2-PE naturally with low yield. Recent metabolic engineering strategies in yeasts and Escherichia coli have achieved great success in improving 2-PE bioproduction, including the alleviation of feed-back inhibition, improvement of precursor transport, enhancing activities of crucial enzymes, and reduction of by-products. Here, we review the metabolic engineering strategies applied to microorganisms for increasing bioproduction of 2-PE, address current problems, and propose further improvements.
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5.
Engineering microbial consortia by division of labor.
Roell, GW, Zha, J, Carr, RR, Koffas, MA, Fong, SS, Tang, YJ
Microbial cell factories. 2019;(1):35
Abstract
During microbial applications, metabolic burdens can lead to a significant drop in cell performance. Novel synthetic biology tools or multi-step bioprocessing (e.g., fermentation followed by chemical conversions) are therefore needed to avoid compromised biochemical productivity from over-burdened cells. A possible solution to address metabolic burden is Division of Labor (DoL) via natural and synthetic microbial consortia. In particular, consolidated bioprocesses and metabolic cooperation for detoxification or cross feeding (e.g., vitamin C fermentation) have shown numerous successes in industrial level applications. However, distributing a metabolic pathway among proper hosts remains an engineering conundrum due to several challenges: complex subpopulation dynamics/interactions with a short time-window for stable production, suboptimal cultivation of microbial communities, proliferation of cheaters or low-producers, intermediate metabolite dilution, transport barriers between species, and breaks in metabolite channeling through biosynthesis pathways. To develop stable consortia, optimization of strain inoculations, nutritional divergence and crossing feeding, evolution of mutualistic growth, cell immobilization, and biosensors may potentially be used to control cell populations. Another opportunity is direct integration of non-bioprocesses (e.g., microbial electrosynthesis) to power cell metabolism and improve carbon efficiency. Additionally, metabolic modeling and 13C-metabolic flux analysis of mixed culture metabolism and cross-feeding offers a computational approach to complement experimental research for improved consortia performance.
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6.
Regulation and metabolic engineering strategies for permeases of Saccharomyces cerevisiae.
Zhang, P, Chen, Q, Fu, G, Xia, L, Hu, X
World journal of microbiology & biotechnology. 2019;(7):112
Abstract
Microorganisms have evolved permeases to incorporate various essential nutrients and exclude harmful products, which assists in adaptation to different environmental conditions for survival. As permeases are directly involved in the utilization of and regulatory response to nutrient sources, metabolic engineering of microbial permeases can predictably influence nutrient metabolism and regulation. In this mini-review, we have summarized the mechanisms underlying the general regulation of permeases, and the current advancements and future prospects of metabolic engineering strategies targeting the permeases in Saccharomyces cerevisiae. The different types of permeases and their regulatory mechanisms have been discussed. Furthermore, methods for metabolic engineering of permeases have been highlighted. Understanding the mechanisms via which permeases are meticulously regulated and engineered will not only facilitate research on regulation of global nutrition and yeast metabolic engineering, but can also provide important insights for future studies on the synthesis of valuable products and elimination of harmful substances in S. cerevisiae.
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7.
Computational Approaches to Design and Test Plant Synthetic Metabolic Pathways.
Küken, A, Nikoloski, Z
Plant physiology. 2019;(3):894-906
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Abstract
Successfully designed and implemented plant-specific synthetic metabolic pathways hold promise to increase crop yield and nutritional value. Advances in synthetic biology have already demonstrated the capacity to design artificial biological pathways whose behavior can be predicted and controlled in microbial systems. However, the transfer of these advances to model plants and crops faces the lack of characterization of plant cellular pathways and increased complexity due to compartmentalization and multicellularity. Modern computational developments provide the means to test the feasibility of plant synthetic metabolic pathways despite gaps in the accumulated knowledge of plant metabolism. Here, we provide a succinct systematic review of optimization-based and retrobiosynthesis approaches that can be used to design and in silico test synthetic metabolic pathways in large-scale plant context-specific metabolic models. In addition, by surveying the existing case studies, we highlight the challenges that these approaches face when applied to plants. Emphasis is placed on understanding the effect that metabolic designs can have on native metabolism, particularly with respect to metabolite concentrations and thermodynamics of biochemical reactions. In addition, we discuss the computational developments that may help to transform the identified challenges into opportunities for plant synthetic biology.
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8.
Improvement of phytochemical production by plant cells and organ culture and by genetic engineering.
Nielsen, E, Temporiti, MEE, Cella, R
Plant cell reports. 2019;(10):1199-1215
Abstract
Plants display an amazing ability to synthesize a vast array of secondary metabolites that are an inexhaustible source of phytochemicals, bioactive molecules some of which impact the human health. Phytochemicals present in medicinal herbs and spices have long been used as natural remedies against illness. Plant tissue culture represents an alternative to whole plants as a source of phytochemicals. This approach spares agricultural land that can be used for producing food and other raw materials, thus favoring standardized phytochemical production regardless of climatic adversities and political events. Over the past 20 years, different strategies have been developed to increase the synthesis and the extraction of phytochemicals from tissue culture often obtaining remarkable results. Moreover, the availability of genomics and metabolomics tools, along with improved recombinant methods related to the ability to overexpress, silence or disrupt one or more genes of the pathway of interest promise to open new exciting possibilities of metabolic engineering. This review provides a general framework of the cellular and molecular tools developed so far to enhance the yield of phytochemicals. Additionally, some emerging topics such as the culture of cambial meristemoid cells, the selection of plant cell following the expression of genes encoding human target proteins, and the bioextraction of phytochemicals from plant material have been addressed. Altogether, the herein described techniques and results are expected to improve metabolic engineering tools aiming at improving the production of phytochemicals of pharmaceutical and nutraceutical interest.
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9.
Common aspects in the engineering of yeasts for fatty acid- and isoprene-based products.
Arhar, S, Natter, K
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2019;(12):158513
Abstract
The biosynthetic pathways for most lipophilic metabolites share several common principles. These substances are built almost exclusively from acetyl-CoA as the donor for the carbon scaffold and NADPH is required for the reductive steps during biosynthesis. Due to their hydrophobicity, the end products are sequestered into the same cellular compartment, the lipid droplet. In this review, we will summarize the efforts in the metabolic engineering of yeasts for the production of two major hydrophobic substance classes, fatty acid-based lipids and isoprenoids, with regard to these common aspects. We will compare and discuss the results of genetic engineering strategies to construct strains with enhanced synthesis of the precursor acetyl-CoA and with modified redox metabolism for improved NADPH supply. We will also discuss the role of the lipid droplet in the storage of the hydrophobic product and review the strategies to either optimize this organelle for higher capacity or to achieve excretion of the product into the medium.
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10.
Advances and future directions in betalain metabolic engineering.
Polturak, G, Aharoni, A
The New phytologist. 2019;(4):1472-1478
Abstract
Betalains are nitrogenous red and yellow pigments found in a single order of plants, the Caryophyllales, and in some higher fungi. They are responsible for the colors observed in many ornamental plants, as well as in various food products, where they are used as natural colorants. Their nutritional properties and attractive colors make them an appealing target for metabolic engineering. This is further heightened by the limited availability of natural betalain sources, arising from their relative scarcity in the plant kingdom, particularly in edible plants. Recent progress in decoding their biosynthetic pathway has facilitated stable heterologous production of betalains in several plant and microbial systems. Here, we provide a brief review of recent advances and discuss current approaches and possible future directions in betalain metabolic engineering, including expanding the chemical diversity of betalains and increasing their yield, exploring new host organisms for their heterologous production, and engineering their secretion from the cell.