莫纳可林的生物合成：红曲霉菌单加氧酶将莫纳可林L转化为莫纳可林J

Biosynthesis of monacolins: conversion of monacolin L to monacolin J by a monooxygenase of Monascus ruber.

作者信息

Komagata D, Shimada H, Murakawa S, Endo A

机构信息

Department of Agricultural and Biological Chemistry, Tokyo Noko University, Japan.

出版信息

J Antibiot (Tokyo). 1989 Mar;42(3):407-12. doi: 10.7164/antibiotics.42.407.

DOI:10.7164/antibiotics.42.407

PMID:2708134

Abstract

The microbial metabolites monacolins J and L are specific inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The producing strain Monascus ruber M 4681 was found to convert exogenously added monacolin L to J. In this hydroxylation reaction 18O2 was incorporated into monacolin L, giving [18O]-monacolin J. The cell-free extracts of M. ruber quantitatively hydroxylated monacolin L to J, and molecular oxygen was required for the hydroxylation. The enzyme was located in the microsomal fraction and specific for NADPH. The enzyme activity was inhibited by metyrapone, carbon monoxide, sulfhydryl reagents and cytochrome c. The results indicate that monacolin L is the precursor of monacolin J, and that a monooxygenase is involved in this reaction.

摘要

微生物代谢产物莫纳可林J和L是3-羟基-3-甲基戊二酰辅酶A还原酶的特异性抑制剂，该酶是胆固醇合成中的限速酶。发现产孢红曲霉菌株M 4681可将外源添加的莫纳可林L转化为J。在该羟基化反应中，18O2被掺入莫纳可林L中，生成[18O]-莫纳可林J。产孢红曲霉的无细胞提取物将莫纳可林L定量羟基化为J，且羟基化反应需要分子氧。该酶定位于微粒体部分，对NADPH具有特异性。该酶活性受到甲吡酮、一氧化碳、巯基试剂和细胞色素c的抑制。结果表明，莫纳可林L是莫纳可林J的前体，且该反应涉及一种单加氧酶。