Sites of the defective enzymes Biosynthetic route Feedback inhibition Feedback repression Control defective

Fig. 3.18. The control of the synthesis of purine nucleotides in a mutant defective m adenylosuccinate synthase and IMP dehydrogenase activities.

„ v rion of mutants that nn. isv'p f' gnizh the presence iji'^umss an, repressors

. -,f auxotrophic mutants has resulted m the ' !K,',on of nianv microbial products in large concen-proJiK obviOUsly, such mutants are not suitable lrilU""S' xnihesis of products which control their own '"' .¡/■sis' independently. A hypothetical example is i\ii i" • ¡g- 19 wherc ,he end Product P contr°ls its hilissnthesis by feedback inhibition of the first "m/vihc ,lhe pathway. If it is required to produce the ■niK'ili.iie F in large concentrations then this may be ■"hiewd b>' the isolation of a mutant auxotrophic for p hi. Jked between F ami P. However, if P is required to be synthesized in large concentrations it is quite useless to produce an auxotrophic mutant. The solution to tin- problem is to modify the organism such that the first enzyme in the pathway no longer recognizes the presence of inhibiting levels of P. The isolation of mutanis altered in the recognition of control factors lus been achieved principally by the use of two techniques:

Hi The isolationOB of analogue resistant mutants, dii The isolation of revertants.

An .m.ilogue is a compound which is very similar in structure to another compound. Analogues of amino acids and nucleotides are frequently growth inhibitory, and their inhibitory properties may be due to a number ill possible mechanisms. For example, the analogue may be used in the biosynthesis of macromolecules resulting in the production of defective cellular components. In some circumstances the analogue is not incorporated in place of the natural product but interferes with in biosynthesis by mimicing its control properties. For sample, consider the pathway illustrated in Fig. 3.19 where the end product, P, feedback inhibits the first enzyme in the pathway. If P* were an analogue of P 'winch could not substitute for P in biosynthesis) and were m inhibit the first enzyme in a similar way to P, then the biosynthesis of P may be prevented by P* which could result in the inhibition of the growth of the organism.

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