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Bacterial synthetic factories

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Bacteria seeded with synthetic pathways

http://www.rsc.org/chemistryworld/2016/04/bacteria-living-chemical-synthesis

 

Chinese scientists have taken a biosynthetic pathway from plants and introduced it into bacteria to create potentially health-boosting chemicals. Their route provides an alternative to complicated chemical syntheses or farming hectares of crops.

Shared photosynthetic components between plant chloroplasts and cyanobacteria make these microbes ideal hosts for expressing foreign plant enzymes. Ping Xu and colleagues at the Shanghai Jiao Tong University have genetically engineered the cyanobacterium Synechococcus elongatusPC7942 with plant-derived enzymes. In total, the team created 18 bacterial strains expressing different combinations of enzymes. The different strains generate a variety of compounds with a six-carbon, phenyl group and three-carbon propene tail, called phenylpropanoids.

Phenylpropanoids perform diverse functions in plants, ranging from ultraviolet light protection to pathogen defence. One such compound, resveratrol, is made when the bacteria express the plant enzyme stilbene synthase downstream of enzymes tyrosine ammonia lyase and 4-coumarate:coenzyme A-ligase. Found in the skin of grapes and other berries, resveratrol reduces the risk of heart disease and is a valuable pharmaceutical commodity. Different versions of the engineered bacteria can also churn out the phenylpropanoid antioxidants caffeic acid, naringenin and coumaric acid.

The Shanghai Jia Tong University team genetically engineered cyanobacteria to produce compounds like flavonoids, stilbenes and curcuminoids usually only found in plants

http://www.rsc.org/chemistryworld/sites/default/files/upload/Photoautotrophic-platform_c6gc00317f-f1_630m.jpg

What’s more, the team added feedback-inhibition resistant enzymes to the bacteria so that the chemical yields would surpass physiological levels. Photosynthesis within the cyanobacteria generates the chemicals from just water, carbon dioxide and a few mineral nutrients.

The bacterial growth medium houses the products, but isolating them at an industrially relevant yield is currently the biggest challenge. However, by not needing to harvest crops, generating the compounds from bacteria is potentially more sustainable. Xu stresses the potential of this point: ‘For the production of 1 tonne of natural resveratrol, our method may save about 485 hectare of farmland at its current production level.’

‘The approach deftly sidesteps major economic challenges by targeting chemicals with high intrinsic value,’ comments Paul Fowler, executive director of the Wisconsin Institute for Sustainable Technology in the US.  A world-scale production plant under these circumstances is not a pre-requisite for commercialising this research.’

 REFERENCES

This article is free until 06 June 2016

J Ni et al, Green Chem., 2016, DOI: 10.1039/c6gc00317f

A photoautotrophic platform for the sustainable production of valuable plant natural products from CO2

Jun Ni,ab   Fei Tao,ab   Yu Wang,ab   Feng Yaoab and   Ping Xu
Many plant natural products have remarkable pharmacological activities. They are mainly produced directly by extraction from higher plants, which can hardly keep up with the surging global demand. Furthermore, the over-felling of many medicinal plants has undesirable effects on the ecological balance. In this study, we constructed a photoautotrophic platform with the unicellular cyanobacterium Synechococcus elongatus PCC7942 to directly convert the greenhouse gas CO2 into an array of valuable healthcare products, including resveratrol, naringenin, bisdemethoxycurcumin, p-coumaric acid, caffeic acid, and ferulic acid. These six compounds can be further branched to many other precious and useful natural products. Various strategies including introducing a feedback-inhibition-resistant enzyme, creating functional fusion proteins, and increasing malonyl-CoA supply have been systematically investigated to increase the production. The highest titers of these natural products reached 4.1–128.2 mg L−1 from the photoautotrophic system, which are highly comparable with those obtained by many other heterotrophic microorganisms using carbohydrates. Several advantages such as independence from carbohydrate feedstocks, functionally assembling P450s, and availability of plentiful NADPH and ATP support that this photosynthetic platform is uniquely suited for producing plant natural products. This platform also provides a green route for direct conversion of CO2 to many aromatic building blocks, a promising alternative to petrochemical-based production of bulk aromatic compounds.
Graphical abstract: A photoautotrophic platform for the sustainable production of valuable plant natural products from CO2

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