Titers and productivity of 3-hydroxypropionic acid (3-HP) in engineered E. coli is in the orders of grams per liter, namely 71g/L and 1.8 g/L/h, as reported by Chu et al., 2015 --> http://onlinelibrary.wiley.com/doi/10.1002/bit.25444/abstract ).
However, when 3-HP is produced in engineered Synechococcus elongatus PCC 7942 (http://www.sciencedirect.com/science/article/pii/S1096717615000993) the titer is in the orders of mg/L, namely 665mg/L and 4.25 mg/L/h.
My question is: why is this the case?
The only difference between the two is the source of organic carbon. Cyanobacteria grows on carbon dioxide (and light), while E. coli grows on organic carbon such as glucose or glycogen. Can the source of organic carbon affect the 3-HP expression? Is this due to the fact that CO2 must be fixed from the air while glycogen/glucose is already present in liquid form in the growth medium?
Thank you in advance!
The titer that was achieved in cyanobacteria is actually not bad at all! Utilizing photosynthetically fixed carbon for 3-HP results in a significant drawdown of pyruvate levels, which is competing directly with the Calvin cycle. There are likely many other perturbations being caused by the novel pathway which could be affecting regulation of photosynthetic metabolism. There is a reason the authors chose a more complex b-alanine pathway rather than the more straightforward malanyl Co-A one. Metabolic engineering of phototrophs is much more challenging than in well-understood heterotrophs like E. coli.
Paul D. Boyer and John E. Walker (1997, Chemistry): Elucidation of enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP).
Rudolph Marcus (1992, Chemistry): Electron transfer theory: included application to photosynthesis. [He was at UIUC, Urbana; had attended my course in "Bioenergetics in Photosynthesis"; is currently at Cal Tech in Pasadena, CA.]
Hartmut Michel; Robert Huber; and Johannes Deisenhofer (1988, Chemistry): X-ray structure of bacterial reaction center. [Michel has visited Urbana several times and I have had many conversations with him before and after his prize; I have casually met Deisenhofer, but never Huber. The work was done at Munich, Germany.]
Peter Mitchell (1978, Chemistry ..to check): Oxidative and photosynthetic phosphorylation: chemi-osmotic theory.[The work was done in England, UK]
Robert Burns Woodward (1965, Chemistry): Total synthesis of chlorophyll, vitamin B12, and other natural products.[He was at Harvard University]
Melvin Calvin (1961, Chemistry): Carbon-di oxide assimilation in photosynthesis.[The work was done at Berkeley; Professor Calvin is known to me as he has visited UIUC, and, he is one of the two professors I had applied to do PhD with; the person who discovered 14C (Martin Kamen),that was crucial for Calvin's experiments, is known to me personally.]
Richard Kuhn (1938, Chemistry): carotenoids; vitamins [Germany]
Paul Karrer (1937, Chemistry): Carotenoid structure; flavins; vitamin B2[Germany]
Hans Fischer (1930, Chemistry): Chlorophyll chemistry; hemin synthesis[Germany]
Richard Martin Wilstatter (1915, Chemistry): Chlorophyll purification and structure, carotenoids, etc.[Germany]
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