This ministry soon after the Fall of Constantinople to the Ottoman Empire (1453) took the functions also of the skeuophylax,[2]: 176 taking care of the holy treasures and relics of the Patriarchate, and in this position Manuel clashed with Patriarch Gennadius II of Constantinople on economical issues.
[2] Under the patronage of the secretary of the Ottoman Sultan, Demetrios Kyritzes, Manuel, together with the Great Chartophylax George Galesiotes, influenced the life of the Church of Constantinople for more than twenty years.
[3]: 255 In 1463 he sided with Joasaph I of Constantinople against the request of the politician George Amiroutzes, a Greek nobleman from the former Empire of Trebizond, to marry a second wife because it was a case of bigamy under Christian canon law.
As punishment for his support of Joasaph I, Manuel had his nose cut by order of Sultan Mehmed II.
Manuel was successful in recovering the esteem of sultan Mehmed II,[2] and in 1476 he himself was elected as Patriarch of Constantinople.