RIT 2214，一种由顶头孢霉突变体产生的新型生物合成青霉素。

RIT 2214, a new biosynthetic penicillin produced by a mutant of Cephalosporium acremonium.

作者信息

Troonen H, Roelants P, Boon B

出版信息

J Antibiot (Tokyo). 1976 Dec;29(12):1258-67. doi: 10.7164/antibiotics.29.1258.

DOI:10.7164/antibiotics.29.1258

Abstract

A number of lysine-requiring auxotrophs of Cephalosporium acremonium were investigated for incorporation of side-chain precursors and for accumulation of beta-lactam compounds. One of the auxotrophs, Acremonium chrysogenum ATCC 20389, producing cephalosporin C and penicillin N only if grown in media supplemented with DL-alpha-amino-adipic acid (DL-alpha-AAA), was found to use L-S-carboxymethylcysteine (L-CMC) as a side-chain precursor for the synthesis of a new penicillin (RIT 2214). No corresponding cephalosporin was detected. The penicillin present in the culture filtrate, was concentrated by adsorption on activated carbon and successive column chromatography on Amberlite IRA-68 and Amberlite XAD-4. Final purification was achieved by cellulose column chromatography. RIT 2214 was identified as 6-(D)-[(2-amino-2-carboxy)-ethylthio]-acetamido]-penicillanic acid by spectral analysis, bioactivity spectrum, elucidation of side-chain structure and finally by semisynthesis. Its biological properties were also evaluated.

摘要

对顶头孢霉的一些赖氨酸营养缺陷型菌株进行了研究，以考察其侧链前体的掺入情况以及β-内酰胺化合物的积累情况。其中一种营养缺陷型菌株，即产黄顶头孢霉ATCC 20389，只有在添加了DL-α-氨基己二酸（DL-α-AAA）的培养基中生长时才会产生头孢菌素C和青霉素N，该菌株被发现可利用L-S-羧甲基半胱氨酸（L-CMC）作为侧链前体来合成一种新的青霉素（RIT 2214）。未检测到相应的头孢菌素。将培养滤液中存在的青霉素通过吸附在活性炭上以及随后在Amberlite IRA-68和Amberlite XAD-4上进行柱色谱法进行浓缩。最终通过纤维素柱色谱法实现纯化。通过光谱分析、生物活性谱、侧链结构解析以及最终的半合成，将RIT 2214鉴定为6-(D)-[(2-氨基-2-羧基)-乙硫基]-乙酰胺基]-青霉烷酸。还对其生物学特性进行了评估。