Cordycepin biosynthesis

Our recent studies have shown that during the time of cordycepin biosynthesis, DNA synthesis is completely stopped. When adenosine-U- C is added to cordycepin producing cultures of Cordyceps militaris and the RNA and DNA isolated, the RNA is radioactive, while the DNA is not. Both adenine and guanine isolated from the RNA are radioactive. 

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

The increased rate of ABA biosynthesis in dehydrated leaves can be blocked by inhibitors of transcription, such as actinomycin D and cordycepin [163-165], as well as by cycloheximide, an inhibitor of cytoplasmic protein synthesis [163,165-167]. These results indicate that nuclear gene transcription and cytosolic protein synthesis are required before an increase in ABA biosynthesis can take place. These processes probably account for the lag period prior to ABA accumulation following the onset of stress [94,163]. Water stress and cycloheximide had no effect on the conversion of XAN to ABA [54]. This indicates that the enzymes catalyzing these conversions are constitutively expressed. The most likely step stimulated by dehydration is, therefore, at the level of xanthophyll cleavage, although isomerization of xanthophylls cannot be ruled out. 

Cordycepin, J deoxyadenosine, adenine 9-cordy-ceposide a purine antibiotic synthesized by Cordy-ceps militaris and Aspergillus nidulans (see Nucleoside antibiotics). JM, 251.24, m.p. 225-226 C, [a] —47° (water). As an antimetabolite of adenosine, it inhibits purine biosynthesis, but is not very toxic. It is phosphorylated metabolically to the monophosphate. 

Purine derivatives Pyrrolopyrimidines, e.g., tubercidin, toyocamycin, viomycin, and purine glycosides with unusual sugar moieties, e.g., cordycepin psicofuranin, decoyinin (D 10.4) Inhibitors of nucleic acid biosynthesis... 

Poly A does not exist in an isolated form in the nucleus and must, therefore, be added to preexisting polynucleotide chains. Thus, when hnRNA molecules have been transcribed, they serve as primer for the biosynthesis of their poly A tail at the 3 -end. Inasmuch as they are no poly (dT) or poly (dA) regions in the DNA, it seems clear that poly A is not synthesized by the traditional transcription mechanisms. Moreover, the enzymes that synthesize poly A are sensitive to cordycepin, which has no or little effect on mRNA synthesis. The enzymes responsible for poly A synthesis have been purified to gel electrophoretic homogeneity from calf thymus in Mary Edmonds laboratory [196]. 

Miscellaneous antibiotics - Griseofulvin. the sideromycins and novobiocin known to affect varied processes in bacteria. can be included in this group. Also to be included are a number of antibiotics such as hadacidin. psicofuranine. tubercidin, toyocamycin. sangivamycin. azasering. diazo-oxo-norleucine (DON), cordycepin and mycophenolic acid known to block biosynthesis of some nucleic acid precursors. ... 

The biosynthesis of psicofuranine has been studied by Sugimori and Suhadol-NiK (1965 a and b). Since adenosine was shown to be the direct precursor in the biosynthesis of cordycepin, one biogenetic scheme considered was that of the addition of a Ci unit to carbon atom-1 of ribose in adenosine to form psicofuranine. This Cl unit could arise from formate, formaldehyde, serine or glycine. 

Suhadolnik, R. J., and J. G. Cory Further evidence for the biosynthesis of cordycepin and proof of the structure of 3-deoxyribose. Biochim. et Biophys. Acta 91, 661 (1964 a). 

The biosynthesis of 3 -amino-3 -deoxyadenosine by Helminthosporium has been studied. As with the biosynthesis of 3 -deoxyadenosine (cordycepin), adenosine-... 

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