Heterologous Pathway Engineering

Niu, Wei; Guo, Jiantao; Dien, Steve Van

doi:10.1007/978-3-319-41966-4_3

Cited by 5 publications

(3 citation statements)

References 113 publications

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“…The biosynthetic power of a single microbe is further expanded when enzymes with promiscuous substrate specificity are exposed to molecular species that share the same functional group and similar carbon skeleton to their native substrates. Synthetic pathways can therefore be devised by combining enzymatic activities from different biological sources into a single host strain in order to achieve the synthesis of target molecules that are not endogenous metabolites or are not even natural products (Weeks and Chang, 2011; Niu et al, 2016; Chatsurachai et al, 2012; Campodonico et al, 2014; Niu et al, 2003; Yim et al, 2011). Moreover, synthetic pathways are also explored for natural products in order to provide ingenious solutions to engineering problems that are intrinsic to naturally existing routes (Atsumi et al, 2008; Bogorad et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid

Niu

Kramer

Mueller

et al. 2019

Metabolic Engineering Communications

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1,2-propanediol (1,2-PDO) is an industrial chemical with a broad range of applications, such as the production of alkyd and unsaturated polyester resins. It is currently produced as a racemic mixture from nonrenewable petroleum-based feedstocks. We have reported a novel artificial pathway for the biosynthesis of 1,2-PDO via lactic acid isomers as the intermediates. The pathway circumvents the cytotoxicity issue caused by methylglyoxal intermediate in the naturally existing pathway. Successful E. coli bioconversion of lactic acid to 1,2-PDO was shown in previous report. Here, we demonstrated the engineering of E. coli host strains for the de novo biosynthesis of 1,2-PDO through this pathway. Under fermenter-controlled conditions, the R-1,2-PDO was produced at 17.3 g/L with a molar yield of 42.2% from glucose, while the S-isomer was produced at 9.3 g/L with a molar yield of 23.2%. The optical purities of the two isomers were 97.5% ee (R) and 99.3% ee (S), respectively. To the best of our knowledge, these are the highest titers of 1,2-PDO biosynthesized by either natural producer or engineered microbial strains that are published in peer-reviewed journals.

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Section: Introductionmentioning

confidence: 99%

Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid

Niu

Kramer

Mueller

et al. 2019

Metabolic Engineering Communications

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“…13,24 Other biotechnological methods of alkaloid production have not yet been applied on industrial scale, but have delivered promising results in laboratory experiments: Metabolic pathway engineering, for instance, makes use of the biosynthetic machinery that nature has evolved for the construction of secondary metabolites, but transposes it into production hosts that are more easily cultivated and optimised than the natural source organism. 25,26 Recently, this approach has been used to create transgenic yeast strains that assemble opioids, 27 tetrahydroisoquinolines, 28 or tropanes 29 from simple sugar and amino acid building blocks, in some cases with impressive product titres [ e.g. , 4.6 g L −1 for ( S )-reticuline].…”

Section: Introductionmentioning

confidence: 99%

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

et al. 2021

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“…Some of the native microbial sources of CPSs of interest in this review are listed in Table 1. The expression of natural biosynthetic pathways in heterologous hosts may be preferred for several reasons, including restricted availability of genetic engineering approaches or poor growth properties of the natural host [18]. The use of 'platform cell factories' such as Escherichia coli, Bacillus subtilis, and Corynebacterium glutamicum [17] has the associated advantages of their well-characterized genetic and physiological properties, and a myriad of available gene expression and genome editing tools ( plasmids, promoters, and terminators) [18,19].…”

Section: Introductionmentioning

confidence: 99%

Metabolic engineering of capsular polysaccharides

Williams

Linhardt

Koffas

2018

Emerging Topics in Life Sciences

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With rising concerns about sustainable practices, environmental complications, and declining resources, metabolic engineers are transforming microorganisms into cellular factories for producing capsular polysaccharides (CPSs). This review provides an overview of strategies employed for the metabolic engineering of heparosan, chondroitin, hyaluronan, and polysialic acid — four CPSs that are of interest for manufacturing a variety of biomedical applications. Methods described include the exploitation of wild-type and engineered native CPS producers, as well as genetically engineered heterologous hosts developed through the improvement of naturally existing pathways or newly (de novo) designed ones. The implementation of methodologies like gene knockout, promoter engineering, and gene expression level control has resulted in multiple-fold improvements in CPS fermentation titers compared with wild-type strains, and substantial increases in productivity, reaching as high as 100% in some cases. Optimization of these biotechnological processes can permit the adoption of industrially competitive engineered microorganisms to replace traditional sources that are generally toxic, unreliable, and inconsistent in product quality.

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Heterologous Pathway Engineering

Cited by 5 publications

References 113 publications

Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid

Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

Metabolic engineering of capsular polysaccharides

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