Omura S, Tanaka Y, Mamada H, Masuma R
J Antibiot (Tokyo). 1984 May;37(5):494-502. doi: 10.7164/antibiotics.37.494.
The production of tylosin by Streptomyces fradiae KA-427 in a defined medium was inhibited by ammonium ions and by inorganic phosphate. The production of protylonolide, an early lactonic intermediate of tylosin biosynthesis with the same carbon skeleton as tylosin aglycone, by a mutant of strain KA-427 was also reduced by these two kinds of ions. In contrast, the bioconversion of protylonolide to tylosin by another mutant was less susceptible to ammonium ions but was sensitive to inorganic phosphate. The addition of protylonolide to a culture of S. fradiae KA-427 increased the tylosin yield, suggesting that aglycone synthesis is limiting under the conditions used. When L-valine, L-leucine, L-isoleucine, L-threonine, or the corresponding 2-keto acid was added to the culture medium, the protylonolide titer increased. The addition of [14C]valine gave rise to [14C]protylonolide. 13C NMR spectroscopic analysis revealed that iso-butyrate, which is a valine metabolite, was incorporated into protylonolide at the carbons known to originate from propionate and n-butyrate. Taking account of these findings, the regulation of tylosin biosynthesis in S. fradiae by ammonium ion is discussed in relation to amino acid metabolism.
弗氏链霉菌KA-427在限定培养基中泰乐菌素的产生受到铵离子和无机磷酸盐的抑制。KA-427菌株的一个突变体产生的原泰乐菌素（泰乐菌素生物合成的早期内酯中间体，与泰乐菌素苷元具有相同的碳骨架）也因这两种离子而减少。相比之下，另一个突变体将原泰乐菌素生物转化为泰乐菌素对铵离子不太敏感，但对无机磷酸盐敏感。向弗氏链霉菌KA-427培养物中添加原泰乐菌素提高了泰乐菌素产量，这表明在所使用的条件下苷元合成是受限的。当向培养基中添加L-缬氨酸、L-亮氨酸、L-异亮氨酸、L-苏氨酸或相应的2-酮酸时，原泰乐菌素效价增加。添加[14C]缬氨酸产生了[14C]原泰乐菌素。13C NMR光谱分析表明，缬氨酸代谢产物异丁酸在已知源自丙酸酯和正丁酸酯的碳原子处掺入原泰乐菌素中。考虑到这些发现，结合氨基酸代谢讨论了铵离子对弗氏链霉菌中泰乐菌素生物合成的调控。
