Bio-based production of fuels and industrial chemicals by repurposing antibiotic-producing type I modular polyketide synthases: opportunities and challenges

Yuzawa, Satoshi; Keasling, Jay D.; Katz, Leonard

doi:10.1038/ja.2016.136

Cited by 22 publications

(13 citation statements)

References 38 publications

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“…Secondary metabolites such as polyketides and non-ribosomal peptides (NRPs) have generated significant interest because of their potential use in a wide range of industries including pharmaceuticals, polymers, flavors and fragrances, and natural dyes. [1][2][3] Natural dyes have been used for centuries to color textiles, 4 cosmetics, and food ingredients. 5 Current industrial production of dyes is predominantly achieved via chemical synthesis, which can involve toxic precursors and generate hazardous chemicals as byproducts of the process.…”

Section: Introductionmentioning

confidence: 99%

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

et al. 2019

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“…Furthermore, hybrid PKSs have been constructed from different naturally occurring PKS and expressed in E. coli, which enabled the production of a variety of α -olefins such as propene, pentene and 1-hexane 56 . These results clearly show the potential of engineering PKS for production of hydrocarbons with different chemical structures, by exploiting the high flexibility of PKS modules 57 .…”

Section: Microbial Metabolic Pathways For Hydrocarbon Biosynthesismentioning

confidence: 66%

Barriers and opportunities in bio-based production of hydrocarbons

2018

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Global climate change caused by the accumulation of greenhouse gases (GHGs) has caused concerns regarding the continued reliance on fossil fuels as our primary energy source. Hydrocarbons produced from biomass using microbial fermentation processes can serve as high-quality liquid transportation fuels and may contribute to a reduction in GHG emissions. Here, we discuss the barriers and opportunities for bio-based production of hydrocarbons to be used as diesel and jet fuels and review recent advances in engineering microbes for production of these chemicals. There are two main challenges associated with establishing bio-based hydrocarbon production from cheap feedstocks; lowering the cost of developing efficient and robust microbial cell factories and establishing more efficient routes for biomass hydrolysis to sugars for fermentation. We discuss how to develop novel systems and synthetic biology tools that can enable faster and cheaper construction of microbial cell factories and thereby address the first challenge, as well as recent advances in biomass processing that will likely lead to overcoming the second challenge in the near future.

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“…Moreover, they were regio-, stereospecific, which may alter the release and cyclization nature via swapping (Pinto et al, 2012;Barajas et al, 2015;Tripathi et al, 2016). Further engineering of other processing domains, such as the methyltransferase (MT) domain, should be conducted to utilize their potential to produce novel chemicals (Yuzawa et al, 2017c).…”

Section: Processing and Offloading Domain Engineering Of Pksmentioning

confidence: 99%

Repurposing Modular Polyketide Synthases and Non-ribosomal Peptide Synthetases for Novel Chemical Biosynthesis

Hwang

Lee

Cho

et al. 2020

Front. Mol. Biosci.

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In nature, various enzymes govern diverse biochemical reactions through their specific three-dimensional structures, which have been harnessed to produce many useful bioactive compounds including clinical agents and commodity chemicals. Polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are particularly unique multifunctional enzymes that display modular organization. Individual modules incorporate their own specific substrates and collaborate to assemble complex polyketides or non-ribosomal polypeptides in a linear fashion. Due to the modular properties of PKSs and NRPSs, they have been attractive rational engineering targets for novel chemical production through the predictable modification of each moiety of the complex chemical through engineering of the cognate module. Thus, individual reactions of each module could be separated as a retro-biosynthetic biopart and repurposed to new biosynthetic pathways for the production of biofuels or commodity chemicals. Despite these potentials, repurposing attempts have often failed owing to impaired catalytic activity or the production of unintended products due to incompatible protein-protein interactions between the modules and structural perturbation of the enzyme. Recent advances in the structural, computational, and synthetic tools provide more opportunities for successful repurposing. In this review, we focused on the representative strategies and examples for the repurposing of modular PKSs and NRPSs, along with their advantages and current limitations. Thereafter, synthetic biology tools and perspectives were suggested for potential further advancement, including the rational and large-scale high-throughput approaches. Ultimately, the potential diverse reactions from modular PKSs and NRPSs would be leveraged to expand the reservoir of useful chemicals.

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Bio-based production of fuels and industrial chemicals by repurposing antibiotic-producing type I modular polyketide synthases: opportunities and challenges

Cited by 22 publications

References 38 publications

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products inR. toruloidesto include non-ribosomal peptides

Barriers and opportunities in bio-based production of hydrocarbons

Repurposing Modular Polyketide Synthases and Non-ribosomal Peptide Synthetases for Novel Chemical Biosynthesis

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