Seno E T, Baltz R H
Antimicrob Agents Chemother. 1982 May;21(5):758-63. doi: 10.1128/AAC.21.5.758.
A series of mutants of Streptomyces fradiae selected for increased production of the macrolide antibiotic tylosin was analyzed for levels of expression of macrocin O-methyltransferase, the enzyme which catalyzes the final step in the biosynthesis of tylosin. Increased tylosin production was accompanied by increased macrocin O-methyltransferase in some of the mutants. Increased expression of macrocin O-methyltransferase was due to more rapid early biosynthesis of the enzyme, to reduced decay of enzyme specific activity late in the fermentation, or to combinations of both. Mutant strains which showed rapid loss of enzyme specific activity late in the fermentation converted large amounts of tylosin to relomycin. The most productive mutants, which synthesized elevated levels of macrocin O-methyltransferase, also produced large amounts of macrocin, the substrate for the enzyme. Incomplete conversion of macrocin to tylosin by these mutants may be due to substrate and product inhibition (E. T. Seno and R. H. Baltz, Antimicrob. Agents Chemother. 20:370-377, 1981). The results suggest that both the levels of precursors and the levels of expression of tylosin biosynthetic enzymes are important for efficient production of tylosin.
对一系列为提高大环内酯类抗生素泰乐菌素产量而筛选出的弗氏链霉菌突变体，分析了大环菌素O -甲基转移酶（催化泰乐菌素生物合成最后一步的酶）的表达水平。在一些突变体中，泰乐菌素产量的增加伴随着大环菌素O -甲基转移酶的增加。大环菌素O -甲基转移酶表达的增加是由于该酶早期生物合成更快、发酵后期酶比活性的衰减减少，或两者兼而有之。在发酵后期显示出酶比活性快速丧失的突变菌株将大量泰乐菌素转化为relomycin。产量最高的突变体合成了高水平的大环菌素O -甲基转移酶，也产生了大量该酶的底物大环菌素。这些突变体未能将大环菌素完全转化为泰乐菌素可能是由于底物和产物抑制作用（E.T. 塞诺和R.H. 巴尔茨，《抗菌剂与化疗》20:370 - 377，1981）。结果表明，前体水平和泰乐菌素生物合成酶的表达水平对于泰乐菌素的高效生产都很重要。
