Question

Case scenario

A waste product for cheese making is whey. You have been tasked with finding a use for the whey from Swiss cheese (aside from a dietary supplement for humans). You isolate a microbe that is genetically related to Lactobacillus. This microbe is able to grow exceptionally well on the whey when you allow for aeration of the culture – it grows weakly without aeration and the pH drops dramatically over time due to an acidic waste product. See Figure 1 and Table 1 for the structure of lactose and the composition of whey. When you sequence the genome you identify genes for Embden Meyerhoff Parnas as well as oxidoreductases and quinones. You also notice it produces an interesting antibiotic when grown in a closed batch system

Table 1. Composition of milk, cheese whev and casein whev % by weight Fat Lactose (milk sugar) Casein protein Whey protein Minerals Minor components Water TOTAL Milk 4.7 4.5 2.7 0.55 0.85 0.20 86.5 100.00 Cheese whey 0.05 5.0 0.10 0.65 0.50 0.30 93.4 100.00

9. Identify which pathway you would target to genetically manipulate to allow for an INCREASE in carbon compounds into the GMP synthesis and divert into INCREASED synthesis of your antibiotic. Please name specific pathways and possible substrates that you would want to try to increase in efforts to maximize your antibiotic output.

Answer 1

The enzyme guanyl cyclase converts GTP into cGMP. GTP is produced in the Kreb' cycle during conversion of succinyl CoA to succinic acid. Succinic acid is further converted to fumaric acid by the enzyme succinate dehydrogenase. When this enzyme is inhibited, more GTP is formed. This can be utilized to synthesize cGMP and divert into increased synthesis of antibiotic.