Some triple mutants, that also over-expressed dox A, were able to double the yield of DXR. This is of more than academic interest, because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum.More efficient production techniques have brought the price down to $1.1 million per kg for the nonliposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps, and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively. Mechanism of action
Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being released and thereby stopping the process of replication. It may also increase quinone type free radical production, hence contributing to its cytotoxicity.The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures.By intercalation, doxorubicin can also induce histone eviction from transcriptionally active chromatin. As a result, DNA damage response, epigenome and transcriptome are deregulated in doxorubicin-exposed cells.
It creates a bony prominence just below the patella, and can be easily located with the fingers. It creates an attachment point for the ligamentum patellae, or patellar ligament. Other tubercles of the tibia include the medial intercondylar tubercle, the lateral intercondylar tubercle, and Gerdys tubercle. Femur
A trochanter is one of up to three tubercles of the femur:

Greater trochanter
Lesser trochanter
Third trochanter, which is occasionally present

Fifth metatarsal
In the fifth metatarsal bone, the most proximal part of the bone is termed the "tuberosity", and the secondary ossification center that is normally present thereon in children is termed the "apophysis". Related diseases and conditions
Fractures
The main type of fracture affecting tubercles is avulsion fracture, by pulling the attached tendon. Apophysitis
Apophysitis is an inflammation of a tubercle. It mainly affects growing children, with overuse of the affected tubercle. Examples include:

Osgood–Schlatter disease (apophysitis of the tibial tubercle)
Severs disease (apophysitis of the posterior tubercle of the heel)
Sinding-Larsen and Johansson syndrome (apophysitis of the inferior pole of the patella)

Enthesitis
Enthesitis is an anatomically close but separate condition, wherein there is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is associated with HLA B27 arthropathies such as ankylosing spondylitis, psoriatic arthritis, and reactive arthritis. == References ==