According to this post - yahoo doesn’t like certain Reply To headers.
I’ve compared my mail headers, see below:
Test mail (=OK)
Received: from mycloud.com (unknown [172.24.0.3])
by myserver.oraclevcn.com (Postfix) with ESMTP id 008BAFD996
for <nextcloudadmin@gmail.com>; Fri, 8 Apr 2022 16:19:29 +0200 (CEST)
Message-ID: <46a2ffd86aa4b51d6466488bc3e7f1d6@mycloud.com>
Subject: Mail test
From: My Cloud <my.cloud@yahoo.com>
To: admin <nextcloudadmin@gmail.com>
MIME-Version: 1.0
Content-Type: multipart/alternative;
boundary="_=_swift_1649427569_1118be7e5e0306759d8028d78f8e50b2_=_"
X-SMTP-MAILFROM: my.cloud@yahoo.com
X-SMTP-RCPTTO: nextcloudadmin@gmail.com
References: <46a2ffd86aa4b51d6466488bc3e7f1d6.ref@mycloud.com>
X-Mailer: WebService/1.1.20001 mail.backend.jedi.jws.acl:role.jedi.acl.token.atz.jws.hermes.yahoo
Content-Length: 15170
Share by mail (bounced with 550 error)
Return-Path: <my.cloud@yahoo.com>
Received: from mycloud.com (unknown [172.24.0.3])
by myserver.oraclevcn.com (Postfix) with ESMTP id 24BACFD9B4
for <user@gmail.com>; Fri, 8 Apr 2022 15:47:28 +0200 (CEST)
Message-ID: <32ced750fc384e5a246175adf17184dc@mycloud.com>
Date: Fri, 08 Apr 2022 13:47:28 +0000
Subject: "admin" voegde een notitie toe aan een bestand dat met jou is
gedeeld
From: admin via My Cloud <my.cloud@yahoo.com>
Reply-To: admin <nextcloudadmin@gmail.com>
To: admin@gmail.com
MIME-Version: 1.0
Content-Type: multipart/alternative;
boundary="_=_swift_1649425648_db2e47324bf516359e593dd241515197_=_"
In the failed mail I do see a Reply-To mailadres which is different than the mail that the mail is send from. Maybe this causes the 550 mailbox unavailable error?
If so, this could be possibly solved by adding a fixed Reply-To header with the nextcloud mailadres (in my example my.cloud@yahoo.com)?
(I don’t know whether this is possible but I assume it is)
Edit:
I’ve checked with my other Nextcloud instance which is installed natively and also uses postfix.
When sending a mail by share by mail I notice that the Reply-To is indeed the mailadres used by Nextcloud to send the mails (instead of the mailadres of the user sharing the file. Thus guess the solution is indeed to somehow change the Reply-To headers?
Date: Fri, 08 Apr 2022 18:26:57 +0000
Subject: share by mail
From: user via Other-Cloud <other.cloud@yahoo.com>
Reply-To: user <other.cloud@yahoo.com>
To: otheruser@hotmail.com
MIME-Version: 1.0
Content-Type: multipart/alternative;
boundary="_=_swift_1649442417_0990c404215067f6fb0cde319f5552bb_=_"
References: <0de5c8a424b825165d7ef13378e1ba40.ref@wouter.servebeer.com>
X-Mailer: WebService/1.1.20001 mail.backend.jedi.jws.acl:role.jedi.acl.token.atz.jws.hermes.yahoo
Content-Length: 19904
Edit 2:
Seems that I was right. I used this to replace my Reply-To headers in my mail with the Nextcloud-mail address & now I don’t receive any 550 error anymore but 250 OK 
Only downside is that the mails are delivered to the spam box from the recipient, but guess this is due to the nature of the automatically send mail.
I’ll send another post with the full solution of my 2 problems, guess it can help others who are using free mail services.
kr