diff --git a/gfa_core/extension_stage_lightweight/runtime_binding.py b/gfa_core/extension_stage_lightweight/runtime_binding.py
index 2478c101f..135a6d240 100644
--- a/gfa_core/extension_stage_lightweight/runtime_binding.py
+++ b/gfa_core/extension_stage_lightweight/runtime_binding.py
@@ -1536,6 +1536,20 @@ def _shell_word_pattern(literal: str) -> re.Pattern[str]:
     )
 
 
+def _shell_word_replacement(replacement: str) -> Callable[[re.Match[str]], str]:
+    """替换函数：保留原文中字面量自带的引号。
+
+    ``shlex.quote`` 在 shell 上下文是正确的，但 ``python -c "...'a.fa'..."`` 里的
+    字符串字面量替换后必须保留引号，否则会变成裸标识符导致 NameError。
+    """
+
+    def _replace(match: re.Match[str]) -> str:
+        quote = match.group("quote") or ""
+        return f"{quote}{replacement}{quote}"
+
+    return _replace
+
+
 def _script_positional_args(contract: dict[str, Any], script: str) -> list[str]:
     try:
         tokens = shlex.split(str(contract.get("original_command") or ""))
@@ -1710,7 +1724,7 @@ def _render_script_updates(
                     "PATCH_TARGET_INVALID", f"invalid match count for {literal}"
                 )
             updated, count = _shell_word_pattern(literal).subn(
-                shlex.quote(replacement), text
+                _shell_word_replacement(replacement), text
             )
             if count < expected:
                 raise RuntimeBindingError(
diff --git a/tests/unit/test_extension_stage_lightweight_runtime_package.py b/tests/unit/test_extension_stage_lightweight_runtime_package.py
index fd46309d2..4015f0ef0 100644
--- a/tests/unit/test_extension_stage_lightweight_runtime_package.py
+++ b/tests/unit/test_extension_stage_lightweight_runtime_package.py
@@ -1528,3 +1528,31 @@ def test_replay_isolates_symlink_input_before_source_overwrite(
         }
     ]
     assert result["execution_work_tree"]["Ft.input.txt"]["type"] == "regular"
+
+
+def test_shell_word_replacement_preserves_python_string_literal_quotes() -> None:
+    """zh01 回归：python -c 里带引号的输出路径被前缀替换后必须保留引号。
+
+    替换前：SeqIO.write(...,'combined.pep.fasta','fasta')
+    若用 shlex.quote 替换会变成 SeqIO.write(...,output.fasta,'fasta')
+    → Python 报 NameError: name 'output' is not defined。
+    """
+    pattern = runtime_module._shell_word_pattern("combined.pep.fasta")
+    replace = runtime_module._shell_word_replacement("output.fasta")
+    source = (
+        "python -c \"from Bio import SeqIO; "
+        "SeqIO.write(list(SeqIO.parse('Ft.SPL.pep.fasta','fasta')),"
+        "'combined.pep.fasta','fasta')\" && "
+        "muscle -in combined.pep.fasta -out combined.pep.mfa"
+    )
+    updated, count = pattern.subn(replace, source)
+    assert count == 2
+    assert "'output.fasta'" in updated
+    assert "'combined.pep.fasta'" not in updated
+    # 无引号的 shell 单词路径不受影响（不引入引号）
+    shell_text = "muscle -in combined.pep.mfa -out combined.pep.mfa2"
+    updated_shell, shell_count = runtime_module._shell_word_pattern(
+        "combined.pep.mfa"
+    ).subn(runtime_module._shell_word_replacement("output.mfa"), shell_text)
+    assert shell_count == 1
+    assert "-in output.mfa" in updated_shell