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Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger

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(1)Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger Mulder, H.J.. Citation Mulder, H. J. (2010, February 2). Unraveling the stepwise activation mechanism of HacA, the key regulator of the unfolded protein response in Aspergillus niger. Retrieved from https://hdl.handle.net/1887/14647 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/14647. Note: To cite this publication please use the final published version (if applicable)..

(2)  Chapter5     GeneralDiscussion.

(3) Chapter5. GeneralDiscussion  —‡–‘–Š‡‹”ƒ–—”ƒŽ ƒ’ƒ„‹Ž‹–›–‘•‡ ”‡–‡Žƒ”‰‡ƒ‘—–•‘ˆ‡œ›‡•‹–‘–Š‡‹”‡˜‹”‘‡–ǡ ˆ‹Žƒ‡–‘—• ˆ—‰‹ Ž‹‡ Aspergillus niger ƒ† Trichoderma reesei ƒ”‡ ‹’‘”–ƒ– ’”‘–‡‹ ’”‘†— –‹‘ Š‘•–• ˆ‘” –Š‡ ‹†—•–”›Ǥ ”‘†— –‹‘ Ž‡˜‡Ž• ‘ˆ ƒ–—”ƒŽ ‡œ›‡• ˆ”‘ –Š‡•‡ ‘”‰ƒ‹•• ƒ ”‡ƒ Š —’ –‘ ͶͲ ‰ȀŽ ƒ† ‹ Ž—†‡ ƒ›Žƒ•‡•ǡ ‡ŽŽ—Žƒ•‡•ǡ š›Žƒƒ•‡•ǡ Ž‹’ƒ•‡•ǡ ’”‘–‡ƒ•‡•ƒ†‘š‹†ƒ•‡•Ǥ

(4)  ‘–”ƒ•–ǡ’”‘†— –‹‘‘ˆŠ‡–‡”‘Ž‘‰‘—•’”‘–‡‹•ǡ‡•’‡ ‹ƒŽŽ›–Š‘•‡ ‘ˆ‘Ǧˆ—‰ƒŽ‘”‹‰‹ǡ‹•‘ˆ–‡Šƒ’‡”‡†„›Ž‘™’”‘†— –‹‘–‹–‡”•ǡ–›’‹ ƒŽŽ›•‡˜‡”ƒŽ‘”†‡”•‘ˆ ƒ‰‹–—†‡Ž‘™‡” ‘’ƒ”‡†–‘Š‘‘Ž‘‰‘—•’”‘–‡‹•ǤŽ–Š‘—‰Š„‘––Ž‡‡ • ƒ‡š‹•–ƒ–ƒŽŽ •–ƒ‰‡• ‘ˆ ’”‘–‡‹ •›–Š‡•‹• ˆ”‘ –”ƒ• ”‹’–‹‘ –‘ •‡ ”‡–‹‘ Ͷ͹ǡ –Š‡ ‘‘ ƒ••—’–‹‘ ‹• –Šƒ––Š‡ƒ‹„‘––Ž‡‡ ‹•ƒ––Š‡Ž‡˜‡Ž‘ˆ’”‘–‡‹ˆ‘Ž†‹‰ƒ†ƒ–—”ƒ–‹‘‹–Š‡ǡ•‹ ‡ ‘˜‡”‡š’”‡••‹‘‘ˆƒŠ‡–‡”‘Ž‘‰‘—•’”‘–‡‹‹•‘ˆ–‡ƒ ‘’ƒ‹‡†„›ƒ—’”‡‰—Žƒ–‹‘‘ˆ ”‡•‹†‡–ˆ‘Ž†ƒ•‡•ƒ† Šƒ’‡”‘‡•ǤŠ‹•‹•ƒ”‡•’‘•‡‘ˆ–Š‡ ‡ŽŽ–‘–Š‡’”‡•‡ ‡‘ˆ‹ ”‡ƒ•‡† Ž‡˜‡Ž• ‘ˆ —ˆ‘Ž†‡† ’”‘–‡‹• ‹ –Š‡ ǡ ƒ† ‹–• ˆ— –‹‘ ‹• –‘ ƒ‹–ƒ‹ Š‘‡‘•–ƒ•‹• ‘ˆ –Š‡ ˆ— –‹‘•‘ˆ–Š‡ǤŠ‡”‡•’‘•‡‹˜‘Ž˜‡•–Š‡‘‹–‘”‹‰‘ˆ–Š‡ˆ‘Ž†‹‰•–ƒ–—•‘ˆ’”‘–‡‹• ‹ –Š‡  ƒ† –Š‡ –”ƒ•‹••‹‘ ‘ˆ –Š‡ ‹ˆ‘”ƒ–‹‘ –‘ –Š‡ — Ž‡—• ‹ ‘”†‡” –‘ ƒŽ–‡” –Š‡ –”ƒ• ”‹’–‹‘ ‘ˆ ”‡Ž‡˜ƒ– ‰‡‡•Ǥ

(5)  A. niger,

(6) ”‡ ‹• –Š‡ Š‘‘Ž‘‰—‡ ‘ˆ –Š‡ ›‡ƒ•–

(7) ”‡ͳ’ ƒ† ƒƒŽ‹ƒ

(8) ͳǡ ™Š‹ Š ‹• –Š‡ •‡•‘” ‘ˆ —ˆ‘Ž†‡† ’”‘–‡‹• ‹ –Š‡ Ǥ

(9) ”‡ –”ƒ•‹–• ƒ •‹‰ƒŽƒ ”‘••–Š‡‡„”ƒ‡‹ˆ–Š‡ˆ‘Ž†‹‰ ƒ’ƒ ‹–›‘ˆ–Š‡‹•‹•—ˆˆ‹ ‹‡–ƒ†—ˆ‘Ž†‡† ’”‘–‡‹• ƒ ——Žƒ–‡ ‹ –Š‡ ‘’ƒ”–‡–Ǥ Š‡ •‹‰ƒŽ ‹• ”‡ ‡‹˜‡† „› hacA ™Š‹ Š ‹ –—” –”ƒ•‹–•–Š‡•‹‰ƒŽ–‘–Š‡— Ž‡—•Ǥ ‡‘‡™‹†‡–”ƒ• ”‹’–‹‘ƒƒŽ›•‡•Šƒ˜‡•Š‘™–Šƒ– –Š‡ƒˆˆ‡ –•ƒŽƒ”‰‡•‡–‘ˆ‰‡‡•Ͷͺǡ͸͵ǡͳͷͶǤŠ‡”‡ˆ‘”‡ǡ‹– ƒ„‡‡š’‡ –‡†–Šƒ––Š‡ƒ –‹˜ƒ–‹‘ ‘ˆ ƒ ǡ ™Š‹ Š ‹• ‘‡ ‘ˆ –Š‡ ‡› ”‡‰—Žƒ–‘”• ‘ˆ –Š‡ ǡ ‹• –‹‰Š–Ž› ”‡‰—Žƒ–‡†Ǥ Š‹• –Š‡•‹• †‡• ”‹„‡• –Š‡ Šƒ”ƒ –‡”‹•ƒ–‹‘ ‘ˆ –Š‡ A. niger ƒ  ƒ† –Š‡ ”‡‰—Žƒ–‹‘ ‘ˆ ‹–• ƒ –‹˜ƒ–‹‘ ‹ ”‡•’‘•‡–‘•–”‡••Ǥ  CharacterisationofHacA Š‡ ‰‡‡ ‡ ‘†‹‰ ƒ  ™ƒ• Ž‘‡† ˆ”‘ A. niger ˜ƒ”Ǥ awamoriǡ ƒ† •‡“—‡ ‡ ƒƒŽ›•‹• •Š‘™‡† –Šƒ– ‹– ‘Ž› •Šƒ”‡• Ž‹‹–‡† Š‘‘Ž‘‰› ™‹–Š ‹–• ›‡ƒ•– ‘—–‡”’ƒ”–Ǥ Ž› –Š‡  „‹†‹‰†‘ƒ‹•‘ˆ–Š‡’”‘–‡‹•Šƒ˜‡„‡‡ ‘•‡”˜‡†Ǥ͵Ͳ‘ˆ–Š‡͵ͻƒ‹‘ƒ ‹†•‹–Š‡ „‹†‹‰†‘ƒ‹ƒ”‡‹†‡–‹ ƒŽ™‹–Š–Š‡›‡ƒ•– ƒ ͳ’Ǥ‡“—‡ ‡ƒƒŽ›•‹•ƒŽ•‘”‡˜‡ƒŽ‡†–Šƒ––Š‡ hacA‰‡‡’‘••‡••‡•ƒ”ƒ–Š‡”•ƒŽŽ— ‘˜‡–‹‘ƒŽ‹–”‘‘ˆʹͲ–ǡ‹ ‘–”ƒ•––‘–Š‡ʹͷʹ– ‹–”‘‘ˆ–Š‡›‡ƒ•–HAC1‰‡‡Ǥ

(10) •’‹–‡‘ˆ–Š‡Ž‘™•‡“—‡ ‡‹†‡–‹–›ƒ––Š‡ƒ‹‘ƒ ‹†Ž‡˜‡Ž ƒ† –Š‡ •‹œ‡ †‹ˆˆ‡”‡ ‡ ‘ˆ –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ǡ –Š‡ ƒ –‹˜ƒ–‹‘ ‡ Šƒ‹• „› — ‘˜‡–‹‘ƒŽ‹–”‘•’Ž‹ ‹‰‘ˆ–Š‡‡••‡‰‡”•Šƒ•„‡‡”‡ƒ”ƒ„Ž›™‡ŽŽ ‘•‡”˜‡†Ǥ• ‹• –Š‡ ƒ•‡ ˆ‘” –Š‡ ›‡ƒ•– HAC1u ƒ† –Š‡ ƒƒŽ‹ƒ XBP1u ‡••‡‰‡”ǡ ƒ •–ƒ„Ž‡ •–‡ǦŽ‘‘’ •–”— –—”‡‹•’”‡†‹ –‡†ˆ‘”–Š‡— ‘˜‡–‹‘ƒŽ‹–”‘”‡‰‹‘‘ˆ–Š‡A.nigerhacAuǤŠ‡ –™‘ ‹–”‘Ǧ‡š‘ „‘”†‡”• ƒ”‡ ’”‡•‡– ‹ Ž‘‘’• ‘ˆ ͹ — Ž‡‘–‹†‡• ‡ƒ Šǡ ƒ† –Š‡ •‡“—‡ ‡ 110GeneralDiscussion.

(11) Chapter5 ‹†‡–‹–› ‹ –Š‡•‡ Ž‘‘’• ‹• ˜‡”› Š‹‰Š ƒ‘‰ –Š‡ –Š”‡‡ ‡—ƒ”›‘–‡• ȋ•‡‡ ‹‰Ǥ ͵ǡ Šƒ’–‡” ʹȌǡ ‹†‹ ƒ–‹˜‡‘ˆ–Š‡Š‹‰Š•‡Ž‡ –‹‘’”‡••—”‡‘–Š‡ ‘•‡”˜ƒ–‹‘‘ˆ–Š‡ƒ –‹˜ƒ–‹‘‡ Šƒ‹•‘ˆ –Š‡†—”‹‰–Š‡ ‘—”•‡‘ˆ‡˜‘Ž—–‹‘Ǥ‘–—‡š’‡ –‡†Ž›–Š‡”‡ˆ‘”‡ǡƒ•‡“—‡ ‡ƒŽ‹‰‡– ‘ˆ –Š‡ ‹–”‘Ǧ‡š‘ „‘”†‡”• ‘ˆ –Š‡ hacA/hac1 — ‘˜‡–‹‘ƒŽ ‹–”‘ ‘ˆ •‡˜‡”ƒŽ ˆ—‰ƒŽ •’‡ ‹‡•ǡ •Š‘™• –Šƒ– ‹–• •‡“—‡ ‡ ‹• ƒŽ‘•– ‹†‡–‹ ƒŽ ‹ •‡˜‡ Aspergilliǡ Fusarium graminearumǡMagnaporthegriseaƒ†T.reeseiȋ ‹‰ǤͳȌǤ   Excisedfragment. A.clavatus  A.flavus  A.fumigatus A.nidulans  A.niger  A.oryzae  A.terreus  F.graminearum M.grisea  T.reesei . v v tcctgcagcggtgttgtg---cgacctgcagtg tcctgcagcggtgttgtg---tgacctgcagtg tcctgcagcggtgttgtg---cgacctgcagtg tcctgcagcgatgttgtg---cgacctgcagtg tcctgcagcggtgttgtg---cgacctgcagtg tcctgcagcggtgttgtg---tgacctgcagtg tcctgcagcgatgttgtg---tgacctgcagtg tcctgccgcgatgttgtc---tgacctgcagtg tcctgccgagatgttgtgcaccgacctgcagtg tcctgcagagatgttgtg---cgacccgcagtg. Figure 1. Ž‹‰‡– ‘ˆ –Š‡ hacA/hac1 — ‘˜‡–‹‘ƒŽ ‹–”‘• ˆ”‘ •‡˜‡ Aspergilliǡ ’Ž—• F. graminearumǡM.griseaǡƒ†T.reeseiǤŠ‡‹–”‘„‘”†‡”•ƒ†–Š‡‡š ‹•‡†ˆ”ƒ‰‡–ƒ”‡‹†‹ ƒ–‡† „›ƒ””‘™•Ǥ.   ‡‘˜ƒŽ ‘ˆ –Š‡ ʹͲ – — ‘˜‡–‹‘ƒŽ ‹–”‘ ˆ”‘ –Š‡ hacA  Šƒ‰‡• –Š‡ ”‡ƒ†‹‰ ˆ”ƒ‡ ‘ˆ –Š‡ –”ƒ• ”‹’– ȋ ‹‰Ǥ ʹȌǤ • ƒ ‘•‡“—‡ ‡ ƒ •ƒŽŽ‡” ’”‘–‡‹ ‹• ‡ ‘†‡† ‹ –Š‡ •’Ž‹ ‡† –”ƒ• ”‹’–Ǥ Š‡”‡ƒ• hacAu ‡ ‘†‡• ƒ ’”‘–‡‹ ‘ˆ Ͷ͵͸ ƒ‹‘ ƒ ‹†•ǡ hacAi ‡ ‘†‡• ƒ ’”‘–‡‹ ‘ˆ ͵Ͷʹ ƒ‹‘ ƒ ‹†•Ǥ ‘–Š ’”‘–‡‹• •Šƒ”‡ǡ Š‘™‡˜‡”ǡ –Š‡ •ƒ‡ Ǧ–‡”‹ƒŽ ’ƒ”– ‘–ƒ‹‹‰–Š‡„‹†‹‰†‘ƒ‹ƒ†–Š‡Ž‡— ‹‡Ǧœ‹’’‡”†‘ƒ‹ǤŠ‹••’Ž‹ ‹‰Ǧ‹†— ‡† ˆ”ƒ‡•Š‹ˆ–‹••‹‹Žƒ”–‘–Š‡ƒ –‹˜ƒ–‹‘‡ Šƒ‹•‘ˆ–Š‡ƒƒŽ‹ƒXBP1Ǥ’Ž‹ ‹‰‘ˆ–Š‡ ʹ͸–‹–”‘ˆ”‘–Š‡ƒƒŽ‹ƒXBP1ƒŽ•‘”‡•—Ž–•‹ƒˆ”ƒ‡•Š‹ˆ–Ǥ ‘™‡˜‡”ǡ–Š‡–”ƒ•Žƒ–‡† ’”‘–‡‹ ˆ”‘ –Š‡ •’Ž‹ ‡† XBP1i –”ƒ• ”‹’– ‹• •‹‰‹ˆ‹ ƒ–Ž› Žƒ”‰‡” –Šƒ ˆ”‘ –Š‡ —•’Ž‹ ‡† XBP1u Ǥ

(12)  ›‡ƒ•–ǡ –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ ‘ˆ HAC1 †‘‡• ‘– ”‡•—Ž– ‹ ƒ ˆ”ƒ‡•Š‹ˆ–ǡ„—– ‘’Ž‡–‡Ž›”‡’Žƒ ‡•–Š‡͵ǯǦ‡†‘ˆ–Š‡–”ƒ• ”‹’–Ǥ‡•’‹–‡–Š‡†‹ˆˆ‡”‡ ‡•ǡ–Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ ƒ†ǡ ƒ• ƒ ”‡•—Ž–ǡ –Š‡ ‡ ‘†‡† ƒ  ’”‘–‡‹ •Šƒ”‡• •‘‡ ˆ‡ƒ–—”‡•™‹–Š„‘–Š–Š‡›‡ƒ•–HAC1ƒ†ƒƒŽ‹ƒXBP1‡ Šƒ‹•‘ˆƒ –‹˜ƒ–‹‘Ǥ. GeneralDiscussion111.

(13) Chapter5             Figure 2.  ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ ‘ˆ –Š‡ A. niger hacA –”ƒ• ”‹’–Ǥ Š‡ hacAu  ‘–ƒ‹•ƒ ‡ ‘†‹‰ƒͶ͵͸ƒ‹‘ƒ ‹†’”‘–‡‹Ǥ’Ž‹ ‹‰‘ˆ–Š‡ʹͲ–— ‘˜‡–‹‘ƒŽ‹–”‘ ƒ—•‡• ƒ ˆ”ƒ‡•Š‹ˆ–ǡ ™Š‹ Š ”‡•—Ž–• ‹ ƒ •Š‘”–‡”   ‹ –Š‡ hacAi –”ƒ• ”‹’–Ǥ Š‡ ‘”‹‰‹ƒŽ ʹʹʹ ƒ‹‘ ƒ ‹†• †‘™•–”‡ƒ ‘ˆ –Š‡ „

(14)  †‘ƒ‹ ‹ ƒ — ƒ”‡ ”‡’Žƒ ‡† „› ͳʹͺ ƒ‹‘ ƒ ‹†• ‹ –Š‡ ƒ ‹’”‘–‡‹Ǥ

(15) ƒ††‹–‹‘–‘–Š‡”‡‘˜ƒŽ‘ˆ–Š‡ʹͲ–‹–”‘ǡ–Š‡hacAi–”ƒ• ”‹’–‹–”— ƒ–‡†ƒ– ‹–•ͷǯǦ‡††—‡–‘–”ƒ• ”‹’–‹‘ˆ”‘ƒ‡™•–ƒ”–•‹–‡—’‘•‡ ”‡–‹‘•–”‡••Ǥ.   DeletionoftheA.nigerhacA ‡Ž‡–‹‘ ‘ˆ hacA ‹ A. niger ”‡•—Ž–‡† ‹ ƒ •‡˜‡”‡ ’Š‡‘–›’‡ǡ ‹†‹ ƒ–‹‰ –Š‡ ‹’‘”–ƒ ‡ ‘ˆ hacAˆ‘”–Š‡ˆ—‰—•ȋ•‡‡ ‹‰ǤͳǡŠƒ’–‡”ͶȌǤŠ‡'hacA•–”ƒ‹‰”‘™•’‘‘”Ž›‘˜ƒ”‹‘—•‡†‹ƒ ƒ† Šƒ”†Ž› ’”‘†— ‡• ƒ› ‘‹†‹ƒǡ ƒ‹‰ –Š‡ Šƒ†Ž‹‰ ‘ˆ –Š‡ •–”ƒ‹ †‹ˆˆ‹ —Ž–Ǥ

(16)  ‘”†‡” –‘ ‘’‡ ™‹–Š •‡ ”‡–‹‘ •–”‡••ǡ hacA ‡˜‡ ƒ’’‡ƒ”‡† –‘ „‡ ‡••‡–‹ƒŽ ƒ• ‰”‘™–Š ™ƒ• ƒ„‘Ž‹•Š‡† —’‘–—‹ ƒ› ‹–”‡ƒ–‡–Ǥ Š‡ •‡˜‡”‡ ’Š‡‘–›’‡ ‘ˆ –Š‡ A. niger 'hacA •–”ƒ‹ ‹• ‹ ‘–”ƒ•– ™‹–Š –Š‡ ”‡ ‡–Ž› ’—„Ž‹•Š‡†A.fumigatus 'hacA—–ƒ–ǤŽ–Š‘—‰Š ‘‹†‹ƒ–‹‘ ™ƒ•†‡ ”‡ƒ•‡†ǡ–Š‡‰”‘™–Š‘ˆ –Š‡A.fumigatus 'hacA•–”ƒ‹™ƒ• ‘’ƒ”ƒ„Ž‡–‘–Š‡™‹Ž†–›’‡•–”ƒ‹‹–Š‡ƒ„•‡ ‡‘ˆ •–”‡•• ͳ͵ʹǤŠ‡ ƒ—•‡ˆ‘”–Š‹•†‹ˆˆ‡”‡ ‡‹’Š‡‘–›’‡„‡–™‡‡–Š‡A.nigerƒ†A.fumigatus. 'hacA—–ƒ–•‹•‘– Ž‡ƒ”Ǥ

(17) – ‘—Ž†ˆ‘”‡šƒ’Ž‡‹†‹ ƒ–‡ƒ†‹•–‹ –†‹ˆˆ‡”‡ ‡‹–Š‡hacA †‡’‡†‡–’ƒ–Š™ƒ›„‡–™‡‡„‘–ŠAspergilliǡ„—–‹‰Š–ƒŽ•‘„‡ƒƒ”–‡ˆƒ –‘ˆ–Š‡‡–Š‘†‘ˆ •–”ƒ‹ ‘•–”— –‹‘Ǥ Ž–Š‘—‰Š †‹ˆˆ‡”‡– ‹ –Š‡ ƒ„•‡ ‡ ‘ˆ •‡ ”‡–‹‘ •–”‡••ǡ „‘–Š 'hacA —–ƒ–••Šƒ”‡–Š‡•‡•‹–‹˜‹–›–‘•–”‡••Ǥ ”‘™–Š™ƒ•ƒŽ•‘ˆ‘—†–‘„‡ƒ„‘Ž‹•Š‡†‹–Š‡A. fumigatus 'hacA•–”ƒ‹ƒ– ‘ ‡–”ƒ–‹‘•‘ˆƒ†–—‹ ƒ› ‹–Šƒ– ‘—Ž†„‡–‘Ž‡”ƒ–‡† „›™‹Ž†–›’‡Ǥ   112GeneralDiscussion.

(18) Chapter5 TheUPRE ƒ ‹ „‹†• –‘ • ’”‡•‡– ‹ –Š‡ ’”‘‘–‡”• ‘ˆ ‹–• –ƒ”‰‡– ‰‡‡•Ǥ Š‡ Aspergillus  ™ƒ•‹†‡–‹ˆ‹‡†ƒ•ƒ’ƒ”–Ž›’ƒŽ‹†”‘‹ •‡“—‡ ‡ƒ”‘—†ƒ•‹‰Ž‡•’ƒ ‡”— Ž‡‘–‹†‡ǡˆ‘ŽŽ‘™‡† „›ƒŠ‹‰ŠŽ› ‘•‡”˜‡†Ǧ•–”‡– Šȋ ‹‰Ǥ͵ȌǤ      Figure3.‡“—‡ ‡Ž‘‰‘‘ˆ–Š‡A.niger ǡ„ƒ•‡†‘ƒƒŽ‹‰‡–‘ˆ–Š‡•‹†‡–‹ˆ‹‡†‹ –Š‡ ’”‘‘–‡”• ‘ˆ bipA, cypB, pdiA, prpA, tigAǡ ƒ† hacAǤ Š‡ „ƒ•‡• ‘ˆ –Š‡ ‘•‡”˜‡† ‘”‡ ƒ”‡ —„‡”‡†—†‡”‡ƒ–Š–Š‡•‡“—‡ ‡ǡƒ†–Š‡•’ƒ ‡”— Ž‡‘–‹†‡‹•Ž‘ ƒ–‡†ƒ–’‘•‹–‹‘ͶǤ.   Š‡•ƒ”‡”‡ƒ”ƒ„Ž›™‡ŽŽ ‘•‡”˜‡†ƒ‘‰Š‘‘Ž‘‰‘—•‰‡‡•‹˜ƒ”‹‘—•AspergilliǤ ‘”‡šƒ’Ž‡ǡ–Š‡ ‘”‡Ǧ•‡“—‡ ‡‘ˆ–Š‡prpA•‘ˆA.nigerǡA.nidulansǡƒ†A.fumigatus ƒ”‡ ‹†‡–‹ ƒŽ ȋ•‡‡ ‹‰Ǥ ͳǡ Šƒ’–‡” ͵ȌǤ ‡“—‡ ‡ ƒŽ‹‰‡– ‘ˆ Žƒ”‰‡” ’”‘‘–‡” ˆ”ƒ‰‡–• •Š‘™• –Šƒ– — Š ‘”‡ ˜ƒ”‹ƒ–‹‘ ‹• ’”‡•‡– ‘—–•‹†‡ –Š‡ • ȋ•‡‡ ‹‰Ǥ ͳǡ Šƒ’–‡” ͵ȌǤ ‘ ƒ’’ƒ”‡–Ž› –Š‡”‡ Šƒ• „‡‡ •–”‹‰‡– •‡Ž‡ –‹‘ ‘ –Š‡ ’”‡•‡”˜ƒ–‹‘ ‘ˆ –Š‡  ‹ Š‘‘Ž‘‰‘—•‰‡‡•Ǥ ‹ ‡ –Š‡ ˜ƒ”‹‘—• • Šƒ˜‡ †‹ˆˆ‡”‡– „‹†‹‰ ƒˆˆ‹‹–‹‡• ˆ‘” ƒ ‹ ȋ•‡‡ ƒ„Ž‡ ͵ǡ Šƒ’–‡” ͵Ȍ –Š‡ ˜ƒ”‹ƒ–‹‘ ‹ –Š‡ • ‘—Ž† „‡ ƒ ‡ Šƒ‹• –‘ ‡•—”‡ †‹ˆˆ‡”‡–‹ƒŽ —’”‡‰—Žƒ–‹‘‘ˆ–Š‡˜ƒ”‹‘—•–ƒ”‰‡–‰‡‡•ǤŠ‡ˆƒ ––Šƒ–ƒ†‹ˆˆ‡”‡ ‡‹„‹†‹‰ƒˆˆ‹‹–› ƒ ”‡•—Ž– ‹ †‹ˆˆ‡”‡–‹ƒŽ ‡š’”‡••‹‘ ™ƒ• •Š‘™ ™‹–Š ƒ ”‡’‘”–‡” ‰‡‡ ‡š’”‡••‡† ˆ”‘ –Š‡ cypB’”‘‘–‡”–Šƒ–Šƒ†‹–•‘”‹‰‹ƒŽ”‡’Žƒ ‡†„›ƒƒ”–‹ˆ‹ ‹ƒŽȋ•‡‡ ‹‰ǤͷǡŠƒ’–‡” ͵ȌǤŠ‹•‡Ž‡‡–ǡ‘„–ƒ‹‡†„›„‹†‹‰•‹–‡•‡Ž‡ –‹‘ǡ’‘••‡••‡†–Š‡Š‹‰Š‡•–„‹†‹‰ƒˆˆ‹‹–› ˆ‘” ƒ  ȋ•‡‡ ƒ„Ž‡ ͵ǡ Šƒ’–‡” ͵Ȍǡ ƒ† ™Š‡ ’Žƒ ‡† ‹ –Š‡ cypB ’”‘‘–‡” ”‡•—Ž–‡† ‹ ƒ Š‹‰Š‡”‡š’”‡••‹‘‘ˆEǦ‰Ž— —”‘‹†ƒ•‡ ‘’ƒ”‡†–‘–Š‡™‹Ž†–›’‡Ǥ Š‡hacA’”‘‘–‡”‹–•‡Žˆ ‘–ƒ‹•–Š”‡‡•ǡƒ†–Š‡†‹ˆˆ‡”‡–ƒˆˆ‹‹–‹‡•‘ˆ–Š‡•‡ ‡Ž‡‡–•‹‰Š–Šƒ˜‡‡˜‘Ž˜‡†–‘‡•—”‡–Š‡–”ƒ• ”‹’–‹‘ƒŽ•™‹– Š‡ Šƒ‹•ƒ•†‡• ”‹„‡† ‹ Šƒ’–‡” ͶǤ ‡“—‡ ‡ ƒŽ‹‰‡– ‘ˆ –Š‡ hacA ’”‘‘–‡”• ‘ˆ A. nidulans ƒ† A. fumigatus ™‹–Š–Š‡A.nigerhacA’”‘‘–‡”ǡ•Š‘™‡†–Šƒ––Š‡›ƒŽ•‘ ‘–ƒ‹–Š”‡‡•ǡƒ†–Šƒ––Š‡› ƒ”‡ ˜‡”› •‹‹Žƒ” ȋ•‡‡ ‹‰Ǥ ͳǡ Šƒ’–‡” ͵ȌǤ  ‹‰—”‡ Ͷ •Š‘™• ƒ ‡š–‡†‡† ƒŽ‹‰‡– ‘ˆ –Š‡ • ‹†‡–‹ˆ‹‡† ‹ –Š‡ hacA/hac1 ’”‘‘–‡”• ‘ˆ ˆ‘—” ƒ††‹–‹‘ƒŽ Aspergilli •’‡ ‹‡•ǡ F. graminearum, M. grisea,ƒ†T. reeseiǤ

(19) ƒŽŽ’”‘‘–‡”•–Š”‡‡’—–ƒ–‹˜‡•™‡”‡ˆ‘—† ™‹–Š •‡“—‡ ‡ ‹†‡–‹–› –‘ –Š‡ A. niger hacA •Ǥ • ƒ „‡ ‡š’‡ –‡†ǡ –Š‡ •‡“—‡ ‡ ‹†‡–‹–›ƒ‘‰–Š‡Aspergilli•‹•˜‡”›Š‹‰Šǡ™Š‡”‡ƒ•‘”‡˜ƒ”‹ƒ–‹‘‹•’”‡•‡–™Š‡ ‘’ƒ”‹‰ –Š‡ • ‘ˆ ‡˜‘Ž—–‹‘ƒ”› ‘”‡ †‹•–ƒ– ˆ—‰ƒŽ •’‡ ‹‡• –‘ –Š‡ A. niger hacA. GeneralDiscussion113.

(20) Chapter5 •Ǥ ‘™‡˜‡”ǡƒŽ•‘‹–Š‡hacA/hac1•‘ˆF.graminearum,M.griseaƒ†T.reeseiǡ –Š‡ƒŒ‘”‹–›‘ˆ–Š‡”‡•‹†—‡•‘ˆ–Š‡A.niger ‘•‡•—•ƒ”‡’”‡•‡–Ǥ     UPRE1 A.clavatus A.flavus A.fumigatus A.niger A.nidulans A.oryzae A.terreus F.graminearum M.grisea T.reesei. -363 -339 -326 -360 -291 -339 -353 -419 -763 -827. 1 3 5 7 9 actgaccacgctggcctttaaa tgagaccacgttggccttttaa actgaccacgctggccttttaa tctgaccacgttggccttttaa attgaccacgctggcctttaaa tgagaccacgttggccttttaa tctgaccacgctggcctctact aactctcaacgtgtcctcaaga cccaggcaaggtttgctactac cctgtacatactgccctgtcca. -177 -154 -166 -161 -122 -154 -168 -301 -383 -469. 1 3 5 7 9 ttatgacaacgtggcctttgct tgatgacaccgtggcctctgac ttatgccaacgtggctttttct ttatgacacggtggcctgtgtt ctatgacaccgtggcctctgtc tgatgacaccgtggcctctgac gtatgacaccgtggcttctgtc agtgaacagtctgtcctttaca tcagaacagcgtgtcctctctc agaggccactctgtcctcttct. UPRE2 A.clavatus A.flavus A.fumigatus A.niger A.nidulans A.oryzae A.terreus F.graminearum M.grisea T.reesei. UPRE3. . A.clavatus A.flavus A.fumigatus Aniger A.nidulans A.oryzae A.terreus F.graminearum M.griseaȋ” Ȍ T.reesei ‘•‡•—•A.niger. -284 -246 -263 -259 -228 -246 -275 -377 -460 -555. 1 3 5 7 9 tgtgaacac-ctgtccttccgt tttggacac-ttgtcctttcca tctgaacac-ttgtccttttgt taaggacac-ctgtccttcttg tatgaacaa-ctgtcctcttca tttggacac-ttgtcctttcca tgtgaacaa-ctgtccttttcc tccatccaacctgtcctgaaat taatggaaaggtgtcctttggc ttgggttac-gtgtcctcaaga cannntgkcct. Figure4.‡“—‡ ‡ƒŽ‹‰‡–‘ˆ–Š‡•‹†‡–‹ˆ‹‡†‹–Š‡hacA/hac1 ’”‘‘–‡”•‘ˆ–‡ˆ—‰ƒŽ •’‡ ‹‡•Ǥ Š‡ „ƒ•‡• ‘ˆ –Š‡ ‘•‡”˜‡† ‘”‡ ƒ”‡ —„‡”‡† ƒ„‘˜‡ –Š‡ •‡“—‡ ‡Ǥ †‡”‡ƒ–Š –Š‡ •‡“—‡ ‡ƒŽ‹‰‡––Š‡ ‘•‡•—••‡“—‡ ‡‘ˆ–Š‡A.niger‹•‰‹˜‡ƒ•ƒ”‡ˆ‡”‡ ‡ǤŠ‡M. grisea ͵ ‹• ’”‡•‡–‡† ƒ• ”‡˜‡”•‡ ‘’Ž‡‡– ȋ” ȌǤ —„‡”• ‹†‹ ƒ–‡ –Š‡ ’‘•‹–‹‘ ‘ˆ –Š‡ ”‡Žƒ–‹˜‡–‘–Š‡ ‘ˆ–Š‡hacA/hac1 Ǥ. 114GeneralDiscussion.

(21) Chapter5  ThePutativeActivationDomainofHacA

(22) ›‡ƒ•–ǡ

(23) ”‡ͳ’‡†‹ƒ–‡†‹–”‘•’Ž‹ ‹‰”‡‘˜‡•ƒʹͷʹ–‹–”‘–Šƒ–‹ Ž—†‡•–Š‡ ‘†‹‰ ’ƒ”–‘ˆ–Š‡‘•–Ǧ–‡”‹ƒŽͳͲƒ‹‘ƒ ‹†•‘ˆ–Š‡ ƒ ͳ’—’”‘–‡‹ǡƒ†Œ‘‹•ƒͳͺƒ‹‘ ƒ ‹† ‡ ‘†‹‰ ’ƒ”– –‘ –Š‡ –”ƒ• ”‹’– ȋ ‹‰Ǥ ͹ ‹–”‘ȌǤ Š‡•‡ ͳͺ ƒ‹‘ ƒ ‹†• ™‡”‡ ˆ‘—† –‘ ˆ— –‹‘ƒ•ƒƒ –‹˜ƒ–‹‘†‘ƒ‹‘ ƒ ͳ’ͻͺǤ‡“—‡ ‡ƒŽ‹‰‡–‘ˆ–Š‹•ƒ –‹˜ƒ–‹‘†‘ƒ‹ ˆ”‘›‡ƒ•–™‹–Š–Š‡A.nigerHacAi•‡“—‡ ‡”‡˜‡ƒŽ‡†ƒ”‡‰‹‘™‹–Š•‘‡‹†‡–‹–›ȋ ‹‰ǤͷȌǡ „‘–Š„‡‹‰‡‰ƒ–‹˜‡Ž› Šƒ”‰‡†Ǥ     Figure5.Ž‹‰‡–‘ˆ–Š‡ͳͺƒ‹‘ƒ ‹†ƒ –‹˜ƒ–‹‘†‘ƒ‹ˆ”‘–Š‡›‡ƒ•– ƒ ͳ’™‹–Šƒ‹‘ ƒ ‹†ʹ͸ͲǦʹ͹͹ˆ”‘–Š‡A.niger ƒ Ǥ.   ‘ Š‡  ™Š‡–Š‡” — ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ ‘ˆ A. niger hacA ƒŽ•‘ Œ‘‹• ƒ ƒ –‹˜ƒ–‹‘ †‘ƒ‹–‘–Š‡„‹†‹‰†‘ƒ‹ǡ•‡˜‡”ƒŽ–”— ƒ–‡†hacA’”‘–‡‹•™‡”‡‡š’”‡••‡†‹–Š‡. 'hacA•–”ƒ‹ǤŽŽ ‘•–”— –•™‡”‡–ƒ”‰‡–‡†–‘–Š‡’›” Ž‘ —•—•‹‰–Š‡’Žƒ•‹†’Ǧ’›” ȗ ‹ –Š‡ ˜‡ –‘” ‘•–”— –‹‘ ȋŠƒ’–‡” ͶȌǤ ‹ ‡ –”ƒ• ”‹’–‹‘ ‘ˆ hacA ‹• •—„Œ‡ – –‘ ƒ—–‘Ǧ ”‡‰—Žƒ–‹‘ǡ–Š‡–”— ƒ–‡† hacA˜ƒ”‹ƒ–•™‡”‡‡š’”‡••‡†ˆ”‘–Š‡ gpdA ’”‘‘–‡”–‘ ƒŽŽ‘™ ˆ‘” ‡“—ƒŽ •–”‘‰ ‡š’”‡••‹‘Ǥ Ž–Š‘—‰Š ‘– ˆ—ŽŽ› ƒƒŽ›•‡†ǡ ‰”‘™–Š –‡•–• ‘ˆ –Š‡ ˜ƒ”‹‘—• –”ƒ•ˆ‘”ƒ–• ‰ƒ˜‡ ƒ Š‹– –Šƒ–ǡ ƒ– Ž‡ƒ•–ǡ ƒ ’ƒ”– ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹ ‘ˆ ƒ ‹ ‹• ‡ ‡••ƒ”›ˆ‘”‹–•ƒ –‹˜‹–›ȋ ‹‰Ǥ͸ȌǤ•–”ƒ‹Šƒ˜‹‰–Š‡hacA‰‡‡–”— ƒ–‡†ƒ––Š‡•‹–‡‘ˆ–Š‡ — ‘˜‡–‹‘ƒŽ‹–”‘ƒ†–Š—•‡š’”‡••‹‰ ƒ ͳǦʹͳͶ™ƒ•—ƒ„Ž‡–‘‰”‘™‹–Š‡’”‡•‡ ‡‘ˆ –—‹ ƒ› ‹ƒ††‹•’Žƒ›‡†ƒ•‹‹Žƒ”’Š‡‘–›’‡ƒ•‹–•’ƒ”‡–ƒŽ'hacA•–”ƒ‹ǡƒŽ–Š‘—‰Š‹–Šƒ† •Ž‹‰Š–Ž› ‘”‡ ‘‹†‹ƒ †—”‹‰ ‘”ƒŽ ‰”‘™–ŠǤ Š‡ –”— ƒ–‡† ƒˆ–‡” ƒ‹‘ ƒ ‹† ʹͺͲǡ –Š—• Ž‡ƒ˜‹‰–Š‡’—–ƒ–‹˜‡ƒ –‹˜ƒ–‹‘†‘ƒ‹‘–Š‡’”‘–‡‹ǡ•–‹ŽŽ‡ƒ„Ž‡†ƒ•–”ƒ‹ ƒ””›‹‰•— Šƒ ‘•–”— ––‘‰”‘™‹–Š‡’”‡•‡ ‡‘ˆ–—‹ ƒ› ‹Ǥ†‡”•–”‡•• ‘†‹–‹‘•ǡ–Š‡’Š‡‘–›’‡ ‘ˆ–Š‡•–”ƒ‹‡š’”‡••‹‰ ƒ ͳǦʹͺͲƒ’’‡ƒ”•–‘„‡•‹‹Žƒ”–‘™‹Ž†–›’‡Ǥ†‡”‘”ƒŽ‰”‘™–Š ‘†‹–‹‘•ǡŠ‘™‡˜‡”ǡ–Š‹••–”ƒ‹Šƒ•ƒ‘”‡Ǯ™‘‘ŽŽ›ǯƒ’’‡ƒ”ƒ ‡–Šƒ™‹Ž†–›’‡Ǥ

(24) –•Š‘—Ž†„‡ ‘–‡† –Šƒ– –Š‡ –™‘ –”— ƒ–‡† hacA ˜ƒ”‹ƒ–• Žƒ  –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ǡ ƒ† –Š—• ƒ”‡ —ƒ„Ž‡–‘•›–Š‡•‹•‡–Š‡ ƒ —’”‘–‡‹ǤŠ‡‹ƒ„‹Ž‹–›–‘’”‘†— ‡ ƒ —™ƒ•‡ƒ”Ž‹‡”•Š‘™ –‘ ”‡•—Ž– ‹ ƒ †‹•–‹ –‹˜‡ ’Š‡‘–›’‡ ™Š‡ ‰”‘™ ‘ ’Žƒ–‡•ǡ „› ‡š’”‡••‹‰ ƒ ‹–”‘ǦŽ‡•• hacA ‰‡‡ ˆ”‘ ‹– ‡†‘‰‡‘—• ’”‘‘–‡” ȋ•‡‡ ‹‰Ǥ Ͷǡ Šƒ’–‡” ͶȌǤ Š‡ ”‡•—Ž–• ’”‡•‡–‡† Š‡”‡‰‹˜‡ƒ‹†‹ ƒ–‹‘–‘–Š‡’”‡•‡ ‡‘ˆƒƒ –‹˜ƒ–‹‘†‘ƒ‹‹–Š‡Ǧ–‡”‹—•‘ˆ ƒ ‹ǡ •‹‹Žƒ”–‘–Š‡›‡ƒ•–HAC1ƒ –‹˜ƒ–‹‘†‘ƒ‹ǡ„—–‘”‡”‡•‡ƒ” Š‹•‡ ‡••ƒ”›–‘—˜‡‹Ž–Š‡ ‡šƒ –’‘•‹–‹‘ǡƒ–—”‡ƒ†ˆ— –‹‘‘ˆ–Š‡†‘ƒ‹Ǥ GeneralDiscussion115.

(25) Chapter5                    Figure6.‘’ƒ”‹•‘‘ˆ–Š‡’Š‡‘–›’‡•†—”‹‰‘Ǧ•–”‡••ƒ†•‡ ”‡–‹‘•–”‡•• ‘†‹–‹‘•‘ˆA.     . niger•–”ƒ‹•‡š’”‡••‹‰˜ƒ”‹‘—•hacA ‘•–”— –•Ǥ• Š‡ƒ–‹ ‘˜‡”˜‹‡™‘ˆ–Š‡‰‡‡–‹  ‘•–”— –• —•‡† ˆ‘” •–”ƒ‹ ‘•–”— –‹‘ ‹• ‹†‹ ƒ–‡† ‘ –Š‡ Ž‡ˆ– •‹†‡ ‘ˆ –Š‡ ˆ‹‰—”‡Ǥ Š‡ Ž‹‰Š– ‰”‡› „‘š‡• ‹†‹ ƒ–‡–Š‡œ‹’†‘ƒ‹–Šƒ–‹•‹†‡–‹ ƒŽ‹ƒŽŽ ‘•–”— –•ǤŠ‡•ƒŽŽ™Š‹–‡„‘š‹†‹ ƒ–‡•–Š‡ʹͲǦ –— ‘˜‡–‹‘ƒŽ‹–”‘ǡ–Š‡„Žƒ „‘š‡•‹†‹ ƒ–‡–Š‡Ǧ–‡”‹—•‘ˆ ƒ —ǤŠ‡†ƒ”‰”‡›„‘š‡• ‹†‹ ƒ–‡–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹‘ˆ ƒ ‹ǤŠ‡•ƒŽŽ•Šƒ†‡†„‘š‹†‹ ƒ–‡•–Š‡—–ƒ–‡†‹–”‘†—‡ –‘™Š‹ Š–Š‡–”ƒ• ”‹’– ƒ‘–„‡•’Ž‹ ‡†Ǥ‹†‹ ƒ–‡•ͳͲɊ‰ȀŽ–—‹ ƒ› ‹Ǥ.  š’”‡••‹‰–Š‡ hacA‰‡‡™‹–Š–Š‡—–ƒ–‡†ƒ†–Š‡”‡ˆ‘”‡—•’Ž‹ ‡ƒ„Ž‡‹–”‘ȋ•‡‡ ‹‰Ǥͷǡ Šƒ’–‡”Ͷˆ‘”—–ƒ–‹‘•Ȍˆ”‘–Š‡gpdA’”‘‘–‡””‡•—Ž–‡†‹ƒ•‹‹Žƒ”’Š‡‘–›’‡‘’Žƒ–‡• ‘’ƒ”‡†–‘ƒ•–”ƒ‹‡š’”‡••‹‰–Š‡ ‘•–”— –ˆ”‘‹–•‡†‘‰‡‘—•’”‘‘–‡”ȋ ‘’ƒ”‡ ‹‰Ǥ ͸ƒ† ‹‰ǤͶǡŠƒ’–‡”ͶȌǤ‘–Š•–”ƒ‹••Š‘™”‡†— ‡†•’‘”—Žƒ–‹‘‘‹‹ƒŽ‡†‹ƒ’Žƒ–‡• ‘’ƒ”‡† –‘ –Š‡ ™‹Ž† –›’‡ •–”ƒ‹ǡ ƒ† ƒ”‡ ƒ’ƒ„Ž‡ ‘ˆ ‰”‘™‹‰ ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ –—‹ ƒ› ‹ǤŠ‡†‹ˆˆ‡”‡ ‡„‡–™‡‡–Š‡–™‘•–”ƒ‹•‹•–Š‡Žƒ ‘ˆ–”ƒ•Žƒ–‹‘ƒŽƒ––‡—ƒ–‹‘ ‘ˆ hacAu ‹ –Š‡ ’͵ •–”ƒ‹Ǥ Š‡ ‡š’”‡••‡† ˆ”‘ –Š‡ gpdA ’”‘‘–‡”ǡ –Š‡ hacA  Žƒ •–Š‡͵ǯǦƒ†ƒ•ƒ”‡•—Ž– ƒ‘–ˆ‘”–Š‡–”ƒ•Žƒ–‹‘ƒŽ„Ž‘ ’”‡•‡–‹–Š‡ƒ–‹˜‡ hacA‡••‡‰‡”Ǥ•ƒ ‘•‡“—‡ ‡ǡ‘”‡ ƒ —’”‘–‡‹‹‰Š–„‡’”‘†— ‡†‹–Š‡’͵ •–”ƒ‹ǡ „—– ™Š‡–Š‡” –Š‹• Šƒ• ƒ› ‡ƒ•—”ƒ„Ž‡ ‡ˆˆ‡ –• ”‡ƒ‹• ƒ •—„Œ‡ – –‘ ˆ—”–Š‡” ‹˜‡•–‹‰ƒ–‹‘Ǥ ‘™‡˜‡”ǡ–Š‡ˆƒ ––Šƒ–„‘–Š•–”ƒ‹•ƒ”‡ ƒ’ƒ„Ž‡‘ˆ‰”‘™–Š‹–Š‡’”‡•‡ ‡‘ˆ –—‹ ƒ› ‹ǡ ‹ ‘–”ƒ•– –‘ –Š‡ 'hacA •–”ƒ‹ ƒ† –Š‡ ’Ͷ •–”ƒ‹ǡ ‹†‹ ƒ–‡• –Šƒ– ƒ — ‹†‡‡† ˆ—Žˆ‹Ž• ƒ ˆ— –‹‘ ‹ –Š‡ ˆ—‰—• ƒ† ƒ– Ž‡ƒ•– ’ƒ”–Ž› ‡ƒ„Ž‡• –Š‡ ˆ—‰—• –‘ ‘˜‡” ‘‡ –Š‡Žƒ ‘ˆ ƒ ‹Ǥ 116GeneralDiscussion.

(26) Chapter5 Š‡”‡ƒ• –Š‡•‡ –”— ƒ–‹‘ ‡š’‡”‹‡–• ‰ƒ˜‡ ƒ ‹†‹ ƒ–‹‘ –Šƒ– ’ƒ”– ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹ ‘ˆ ƒ ‹ ‹• †‹•’‡•ƒ„Ž‡ ˆ‘” –Š‡ ˆ—‰—• ‹ ‘’‹‰ ™‹–Š  •–”‡••ǡ •‡“—‡ ‡ ƒŽ‹‰‡–•”‡˜‡ƒŽ‡†ƒ ‘•‡”˜‡†’ƒ”–ƒ––Š‡‡†‘ˆ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹•‘ˆ ƒ ‹Ȁ ƒ ͳ‹ ˆ”‘–‡ˆ—‰ƒŽ•’‡ ‹‡•ȋ ‹‰Ǥ͹ȌǤŠ‹•‹‰Š–‹†‹ ƒ–‡–Šƒ–ƒŽ•‘–Š‡‘•–Ǧ–‡”‹ƒŽ’ƒ”–‘ˆ ƒ ‹ˆ—Žˆ‹Ž•ƒ‹’‘”–ƒ–ˆ— –‹‘ȋ‹Ǥ‡Ǥƒ –‹˜ƒ–‹‘†‘ƒ‹‘”„‹†‹‰•‹–‡ˆ‘”‘–Š‡”ˆƒ –‘”• ‘ˆ–Š‡–”ƒ• ”‹’–‹‘‹‹–‹ƒ–‹‘ ‘’Ž‡šȌǤ. Figure7.Ž‹‰‡–‘ˆ–Š‡ƒ‹‘ƒ ‹†•‡“—‡ ‡•‘ˆ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹•‘ˆ ƒ ‹Ȁ ƒ ͳ‹ ˆ”‘ –‡ˆ—‰ƒŽ•’‡ ‹‡•ǤŠ‡ ‘•‡”˜‡†”‡•‹†—‡•ƒ––Š‡Ǧ–‡”‹—•‘ˆ–Š‡–‡ ƒ Ȁ ƒ ͳ’”‘–‡‹•ƒ”‡ ‹†‹ ƒ–‡†„›ƒ•–‡”‹š‡•Ǥ. GeneralDiscussion117.

(27) Chapter5 TheCterminalDomainofHacAu Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹• ‘ˆ ƒ — ˆ”‘ A. nigerǡ A. nidulans ƒ† A. fumigatus ƒ”‡ Š‹‰ŠŽ› ‘•‡”˜‡†ǡ‡˜‡‘”‡–Šƒ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹•‘ˆ–Š‡‹†— ‡† ƒ ‹’”‘–‡‹•ȋ•‡‡ ‹‰Ǥ ͶǡŠƒ’–‡”ʹȌǤŠ‹• ‘—Ž†„‡†—‡–‘ƒ•’‡ ‹ƒŽ‹•‡†›‡–—‘™ˆ— –‹‘–Šƒ– ƒ —Šƒ•‹–Š‡ ˆ—‰—•Ǥ  ‹†‹ ƒ–‹‘ –Šƒ– ƒ — ‹†‡‡† ˆ—Žˆ‹Ž• ƒ ˆ— –‹‘ ‹ –Š‡ ‡ŽŽ ‘‡• ˆ”‘ ƒ •–”ƒ‹ ƒ””›‹‰ƒ‹–”‘ǦŽ‡••˜‡”•‹‘‘ˆ–Š‡hacA‰‡‡ȋ•‡‡ ‹‰ǤͶǡŠƒ’–‡”ͶȌǤŠ‹••–”ƒ‹ ƒ‘– ’”‘†— ‡ ƒ —ǡ ƒ† ƒŽ–Š‘—‰Š ‹– ƒ ‘’‡ ™‹–Š –—‹ ƒ› ‹ •–”‡••ǡ ‹–• ‰”‘™–Š †—”‹‰ ‘Ǧ •–”‡•• ‘†‹–‹‘• ‹• •Ž‹‰Š–Ž› ‹’ƒ‹”‡† ƒ† ‹– ‰‡‡”ƒ–‡• Ž‡•• ‘‹†‹ƒ —†‡” „‘–Š ‘†‹–‹‘• ‘’ƒ”‡† –‘ ™‹Ž† –›’‡Ǥ

(28) – ‹• —‘™ ™Š‡–Š‡” •‹‰‹ˆ‹ ƒ– Ž‡˜‡Ž• ‘ˆ ƒ — ’”‘–‡‹ ™‹ŽŽ „‡ ’”‘†— ‡† ‹ A. nigerǡ „—– ƒ ’‘••‹„Ž‡ ˆ— –‹‘ ˆ‘” ƒ — ™‘—Ž† „‡ –Š‡ ”‘Ž‡ ‘ˆ ƒ ‡‰ƒ–‹˜‡ ”‡‰—Žƒ–‘” ‘ˆ –Š‡ Ǥ

(29)  ƒƒŽ‹ƒ ‡ŽŽ• ‹– ™ƒ• ”‡ ‡–Ž› •Š‘™ –Šƒ– ͳ— ƒ –• ƒ• ƒ ‡‰ƒ–‹˜‡”‡‰—Žƒ–‘”‘ˆͳ‹ƒ† ͸ͳͺͻǤ ‹‹Žƒ” –‘ –Š‡ •’Ž‹ ‹‰ ‘ˆ hacAǡ •’Ž‹ ‹‰ ‘ˆ –Š‡ ʹ͸ – ‹–”‘ ˆ”‘ XBP1 Šƒ‰‡• –Š‡ ”‡ƒ†‹‰ˆ”ƒ‡‘ˆ–Š‡–”ƒ• ”‹’–†‘™•–”‡ƒ‘ˆ–Š‡„‹†‹‰†‘ƒ‹ƒ††‹‡”‹•ƒ–‹‘ †‘ƒ‹ǡ”‡•—Ž–‹‰‹–Š‡•™‹– Š‘ˆƒŽƒ”‰‡’ƒ”–‘ˆ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹Ǥ

(30) –™ƒ•ˆ‘—†–Šƒ– ͳ—•Š—––Ž‡•„‡–™‡‡–Š‡— Ž‡—•ƒ†–Š‡ ›–‘’Žƒ•†—‡–‘ƒ— Ž‡ƒ”‡š Ž—•‹‘•‹‰ƒŽ‹ ‹–• Ǧ–‡”‹ƒŽ †‘ƒ‹Ǥ ͳ— –ƒ”‰‡–• „‘–Š ͳ‹ ƒ†  ͸ ‹ –Š‡ — Ž‡—• „› ƒ••‘ ‹ƒ–‹‰ ™‹–Š –Š‡ǡ ƒ† –ƒ”‰‡–• –Š‡ •—„•‡“—‡–Ž› –‘ –Š‡ ’”‘–‡ƒ•‘‡ ˆ‘” †‡‰”ƒ†ƒ–‹‘Ǥ Š‡–Š‡” •— Š ƒ ˆ— –‹‘ ƒŽ•‘ ”‡•‹†‡• ‹ –Š‡ Ǧ–‡”‹—• ‘ˆ ƒ — ”‡ƒ‹• –‘ „‡ ‡šƒ‹‡†ǡ „—– •‡“—‡ ‡ ƒƒŽ›•‹• ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹ ‘ˆ ƒ — •Š‘™‡† –Šƒ– ‹– ‹• ƒ Ž‡— ‹‡ ”‹ Š †‘ƒ‹Ǥ ˆ –Š‡ ʹʹʹ ƒ‹‘ ƒ ‹†• ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ ƒ — †‘ƒ‹ ͶͲ ƒ”‡ Ž‡— ‹‡ ”‡•‹†—‡•ǡ ƒ ‘—–‹‰ˆ‘”ͳͺΨ‘ˆ–Š‡†‘ƒ‹Ǥ

(31)  ‘’ƒ”‹•‘ǡ–Š‡Ǧ–‡”‹ƒŽ†‘ƒ‹‘ˆ ƒ ‹Šƒ•‘Ž› ͳͳŽ‡— ‹‡”‡•‹†—‡•ǤŠ‹• ‘—Ž†„‡‹†‹ ƒ–‹˜‡‘ˆ–Š‡’”‡•‡ ‡‘ˆƒ— Ž‡ƒ”‡š Ž—•‹‘•‹‰ƒŽ ȋȌ‹–Š‡Ǧ–‡”‹—•‘ˆ ƒ —Ǥǯ•ƒ”‡Ž‡— ‹‡”‹ Š— Ž‡ƒ”‡š’‘”–•‹‰ƒŽ•–Šƒ–‹›‡ƒ•– Šƒ˜‡„‡‡•Š‘™–‘‹–‡”ƒ –™‹–Š–Š‡”ͳ’ȋŠ”‘‘•‘‡‡‰‹‘ƒ‹–‡ƒ ‡’”‘–‡‹ͳȌǡ ƒ — Ž‡ƒ” ‡š’‘”–‹ ͵͵Ǥ

(32)  ƒ††‹–‹‘ǡƒ •‡“—‡ ‡ ƒŽ‹‰‡– ‘ˆ –Š‡ Ǧ–‡”‹ƒŽ †‘ƒ‹• ‘ˆ –‡ ˆ—‰ƒŽ ƒ —Ȁ ƒ ͳ—’”‘–‡‹•ǡ•Š‘™‡†–Šƒ––Š‡›ƒŽŽƒ”‡Ž‡— ‹‡”‹ Šȋ ‹‰ǤͺȌǤ ‹•‹†‡‡†’”‡†‹ –‡†‹–Š‡Ǧ–‡”‹—•‘ˆA.niger ƒ —ȋʹͶͷǡʹͶ͹ǡʹͷ͵Ȍ„› –Š‡‡–ͳǤͳ•‡”˜‡”ȋŠ––’ǣȀȀ™™™Ǥ „•Ǥ†–—Ǥ†Ȁ•‡”˜‹ ‡•Ȁ‡–ȀȌ͹͹ǡ™Š‡”‡ƒ•‘‡ ƒ„‡ ˆ‘—† ‹ ƒ ‹Ǥ Š—• ƒ — ‹‰Š– ™‡ŽŽ ’Žƒ› ƒ ”‘Ž‡ •‹‹Žƒ” –‘ –Š‡ ƒƒŽ‹ƒ ͳ—ǡ ƒ† •Š—––Ž‡„‡–™‡‡–Š‡— Ž‡—•ƒ† ›–‘’Žƒ•‹‘”†‡”–‘–”ƒ•’‘”– ƒ ‹–‘–Š‡’”‘–‡ƒ•‘‡ ˆ‘”†‡‰”ƒ†ƒ–‹‘Ǥ ‘™‡˜‡”ǡ–Š‹• ƒ‘–„‡–Š‡‘Ž›ˆ— –‹‘‘ˆ ƒ —ǡƒ•ȋ‘˜‡”Ȍ‡š’”‡••‹‘ ‘ˆ ƒ —‹–Š‡ƒ„•‡ ‡‘ˆ ƒ ‹’ƒ”–Ž›”‡• —‡•–Š‡’Š‡‘–›’‡‘ˆ–Š‡ 'hacA•–”ƒ‹ȋ ‹‰Ǥͳ ƒ† Ͷǡ Šƒ’–‡” Ͷ ƒ† ‹‰Ǥ ͸ȌǤ Š‡•‡ •–”ƒ‹• ‡š’”‡•• hacA ™‹–Š ƒ —–ƒ–‡† — ‘˜‡–‹‘ƒŽ ‹–”‘ –Šƒ– ƒ ‘– „‡ •’Ž‹ ‡†ǡ ƒ† –Š—• ƒ ‘Ž› ’”‘†— ‡ ƒ — ’”‘–‡‹Ǥ ‹–Š‡” ƒ — †‹”‡ –Ž›‹–‡”ƒ –•™‹–Š’”‘‘–‡”‡Ž‡‡–•ƒ†ƒŽ–‡”•–”ƒ• ”‹’–‹‘‘ˆ†‘™•–”‡ƒ‰‡‡•ǡ‘” ‹– ˆƒ ‹Ž‹–ƒ–‡• –Š‡ — Ž‡ƒ” ‡š’‘”– ȋ„‡•‹†‡• ƒ ‹Ȍ ‘ˆ ‘–Š‡” „

(33)  –”ƒ• ”‹’–‹‘ ˆƒ –‘”• ˆ‘” †‡‰”ƒ†ƒ–‹‘Ǥ. 118GeneralDiscussion.

(34) Chapter5. Figure 8. Ž‹‰‡– ‘ˆ –Š‡ ƒ‹‘ ƒ ‹† •‡“—‡ ‡• ‘ˆ –Š‡ ȋ’ƒ”–‹ƒŽȌ Ǧ–‡”‹ƒŽ †‘ƒ‹• ‘ˆ ƒ —Ȁ ƒ ͳ—ˆ”‘–‡ˆ—‰ƒŽ•’‡ ‹‡•ǤŠ‡ ‘•‡”˜‡†Ž‡— ‹‡”‡•‹†—‡•ƒ”‡‹†‹ ƒ–‡†„›ƒ•–‡”‹š‡•ǡ ™Š‹ Š ‹‰Š– „‡ ‹†‹ ƒ–‹˜‡ ˆ‘” –Š‡ ’”‡•‡ ‡ ‘ˆ ƒ  ‹ –Š‡•‡ †‘ƒ‹•Ǥ ”‘ T. reesei, F. graminearumǡƒ†M.grisea‘Ž›–Šƒ–’ƒ”–‘ˆ–Š‡‹” ƒ ͳ—Ȁ ƒ —’”‘–‡‹•‹••Š‘™–Šƒ–‡šŠ‹„‹–• •‹‰‹ˆ‹ ƒ–Š‘‘Ž‘‰›™‹–Š–Š‡Aspergilli ƒ —’”‘–‡‹•Ǥ. GeneralDiscussion119.

(35) Chapter5 LongRangeBasePairingandtheTranscriptionalSwitch

(36)  ƒ††‹–‹‘ –‘ –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ ™Š‹ Š ‹• ƒ ‘‘ ˆ‡ƒ–—”‡ ƒ‘‰ ‡—ƒ”›‘–‡•ǡ–Š‡hacAi–”ƒ• ”‹’–‹•ʹ͵Ͳ–•Š‘”–‡‡†ƒ–‹–•ͷǯ ‘’ƒ”‡†–‘–Š‡ˆ—ŽŽŽ‡‰–Š hacAu–”ƒ• ”‹’–ǤŠ‹•‹•–Š‡”‡•—Ž–‘ˆ–Š‡•›–Š‡•‹•‘ˆhacAˆ”‘ƒ‡™–”ƒ• ”‹’–‹‘•–ƒ”–ǡ Ž‘•‡”–‘–Š‡•–ƒ”– ‘†‘‘ˆhacAǡƒ†‹•‡†‹ƒ–‡†„› ƒ ‹‹–•‡Žˆƒ†˜‹ƒʹǤ•ƒ”‡•—Ž– ‘ˆ–Š‹•‡™–”ƒ• ”‹’–‹‘ǡˆ‘—”†‹ˆˆ‡”‡–hacA–”ƒ• ”‹’–• ƒ„‡’”‡•‡–‹–Š‡ˆ—‰ƒŽ ‡ŽŽǣ ˆ—ŽŽŽ‡‰–Š—•’Ž‹ ‡†hacAǡˆ—ŽŽŽ‡‰–Š•’Ž‹ ‡†hacAǡ–”— ƒ–‡†—•’Ž‹ ‡†hacAƒ†–”— ƒ–‡† •’Ž‹ ‡†hacA.Š‹•Šƒ••‘‡‹’Ž‹ ƒ–‹‘•Ǥ —‡ –‘ Ž‘‰ ”ƒ‰‡ „ƒ•‡Ǧ’ƒ‹”‹‰ǡ –Š‡ ˆ—ŽŽ Ž‡‰–Š hacA –”ƒ• ”‹’– ‹• •—„Œ‡ – –‘ –”ƒ•Žƒ–‹‘ƒŽ ƒ––‡—ƒ–‹‘ǡ •‹‹Žƒ” –‘ ›‡ƒ•– HAC1u ȋ•‡‡ ‹‰Ǥ ͺǡ Šƒ’–‡” ͳȌ ͳ͵͹Ǥ ‘–”ƒ”› –‘ ›‡ƒ•–ǡ •’Ž‹ ‹‰ ‘ˆ –Š‡ ‹–”‘ †‘‡• ‘– ”‡Ž‹‡˜‡ –Š‡ hacA –”ƒ• ”‹’– ˆ”‘ –Š‡ –”ƒ•Žƒ–‹‘ƒŽ „Ž‘ ȋ ‹‰ǤͻȌǤ•ƒ ‘•‡“—‡ ‡ǡ–Š‡‹‹–‹ƒŽ

(37) ”‡‡†‹ƒ–‡†•’Ž‹ ‹‰‘ˆhacA†‘‡•‘– ‹‡†‹ƒ–‡Ž› –—” ‘ –Š‡ ’ƒ–Š™ƒ› ƒ– ‹–• ˆ—ŽŽ •–”‡‰–ŠǤ Š‡ ˆ—ŽŽ Ž‡‰–Š hacAi –”ƒ• ”‹’– Šƒ• ˆ‹”•––‘‡• ƒ’‡–Š‡–”ƒ•Žƒ–‹‘ƒŽ„Ž‘ ƒ†›‹‡Ž†•—ˆˆ‹ ‹‡– ƒ ‹’”‘–‡‹–Šƒ–•—„•‡“—‡–Ž› ƒ‘’‡”ƒ–‡–Š‡–”ƒ• ”‹’–‹‘ƒŽ•™‹– ŠǤŠ‡‡™Ž›•›–Š‡•‹•‡†–”— ƒ–‡†hacAu–Š‡ ‡‡†•–‘„‡•’Ž‹ ‡†„›

(38) ”‡„‡ˆ‘”‡‹– ƒ ‘–”‹„—–‡–‘–Š‡ ƒ ‹’‘‘ŽǤŠ—•ǡ–Š‡— ‘—’Ž‹‰ ‘ˆ –Š‡ –”ƒ•Žƒ–‹‘ƒŽ „Ž‘  ˆ”‘ –Š‡ — ‘˜‡–‹‘ƒŽ ‹–”‘ •’Ž‹ ‹‰ǡ ‘ˆˆ‡”• A. niger ƒ ƒ††‹–‹‘ƒŽŽ‡˜‡Ž‘ˆ ‘–”‘Ž‹ƒ –‹˜ƒ–‹‘‘ˆ–Š‡’ƒ–Š™ƒ› ‘’ƒ”‡†–‘›‡ƒ•–Ǥ                 Figure 9.  Š‡ƒ–‹  ”‡’”‡•‡–ƒ–‹‘ ‘ˆ –Š‡ •‡ ‘†ƒ”› •–”— –—”‡ ƒ† Ž‘‰ ”ƒ‰‡ „ƒ•‡ ’ƒ‹”‹‰ ‹. –Š‡ A. niger hacAu ǡ ƒ—•‹‰ –”ƒ•Žƒ–‹‘ƒŽ ƒ––‡—ƒ–‹‘Ǥ Š‡ hacA ͷǯ ƒ† hacA ‘†‹‰ •‡“—‡ ‡ ‘–ƒ‹ ‘’Ž‡‡–ƒ”› •‡“—‡ ‡•Ǥ Š‘™ ƒ• †ƒ•Š‡† Ž‹‡• ƒ”‡ –Š‡ — ‘˜‡–‹‘ƒŽ  ‹–”‘ǡƒ†–Š‡’ƒ”–‘ˆ–Š‡ͷǯ–Šƒ–‹•Ž‘•–ˆ”‘–Š‡hacA–”ƒ• ”‹’–—’‘•‡ ”‡–‹‘•–”‡••ǤŠ‡  ‹–”‘„‘”†‡”•ƒ”‡‹†‹ ƒ–‡†„›–Š‡•ƒŽŽŽ‘‘’•ǡ‡–Š‡•’Ž‹ ‡•‹–‡•ƒ”‡‹†‹ ƒ–‡†„›–Š‡ƒ””‘™•Ǥ  Š‡•–‘’ ‘†‘•’”‡•‡–‹–Š‡”‡ƒ†‹‰ˆ”ƒ‡‘ˆhacAuƒ†hacAiƒ”‡‹†‹ ƒ–‡†„›ƒ•–‡”‹š‡•Ǥ. .  120GeneralDiscussion.

(39) Chapter5

(40) ˆ ƒ —‹†‡‡†™‘—Ž†ˆ— –‹‘ƒ•ƒ‡‰ƒ–‹˜‡”‡‰—Žƒ–‘”‘ˆ–Š‡ƒ••’‡ —Žƒ–‡†‡ƒ”Ž‹‡”ǡ–Š‹• –™‘ •–‡’ ƒ –‹˜ƒ–‹‘ ‘ˆ –Š‡  ™‘—Ž† ƒŽ•‘ ‘ˆˆ‡” –Š‡ ˆ—‰—• ƒ ‹‰‡‹‘—• ™ƒ› ‘ˆ “—‹ Ž› •Š—––‹‰ –Š‡ ’ƒ–Š™ƒ› ‘ˆˆǤ ‡ƒ•‹‰ –Š‡

(41) ”‡ †‡’‡†‡– •’Ž‹ ‹‰ ™‘—Ž† Ž‡ƒ˜‡ ƒ ’‘‘Ž ‘ˆ –”— ƒ–‡†„—–—•’Ž‹ ‡†hacA‹–Š‡ ‡ŽŽǤ‘–•—„Œ‡ –‡†–‘–”ƒ•Žƒ–‹‘ƒŽƒ––‡—ƒ–‹‘ǡ –Š‹• ‘—Ž† –Š‡ ”‡ƒ†‹Ž› „‡ –”ƒ•Žƒ–‡† ‹–‘ ƒ — ’”‘–‡‹ ƒ† –ƒ”‰‡– –Š‡ ƒ ‹ ’‘‘Ž ˆ‘” †‡‰”ƒ†ƒ–‹‘ǡ–Š‡”‡„›“—‹ Ž›•–‘’’‹‰—‡ ‡••ƒ”›ƒ –‹˜ƒ–‹‘‘ˆ–ƒ”‰‡–‰‡‡•Ǥ  CpcA

(42)  S. cerevisiae Ͷ’ ’Žƒ›• ƒ ‹’‘”–ƒ– ”‘Ž‡ ‹ –Š‡ ”‡‰—Žƒ–‹‘ ‘ˆ –Š‡  ȋ•‡‡ ‹‰Ǥ ͻǡ Šƒ’–‡”ͳȌǤ”‡˜‹‘—•Ž›™‡•’‡ —Žƒ–‡†‘ƒ”‘Ž‡ˆ‘”’ ‹–Š‡–”ƒ• ”‹’–‹‘ƒŽ”‡‰—Žƒ–‹‘‘ˆ hacAȋ•‡‡ ‹‰Ǥ͸ǡŠƒ’–‡”ͶȌǤ’ ‹•–Š‡A.nigerŠ‘‘Ž‘‰—‡‘ˆ–Š‡›‡ƒ•– Ͷ’ǡƒ†ƒ•ƒ –”ƒ• ”‹’–‹‘ƒŽƒ –‹˜ƒ–‘”‹‰Š–„‡”‡•’‘•‹„Ž‡ˆ‘”–Š‡–”ƒ• ”‹’–‹‘‘ˆ–Š‡ˆ—ŽŽŽ‡‰–ŠhacAǡ ‡˜‡ ™Š‡ ͳ ‹• —–ƒ–‡† ȋ•‡‡ ‹‰Ǥ ͵ǡ Šƒ’–‡” ͶȌǤ  •‡“—‡ ‡ ƒŽ‹‰‡– ‘ˆ hacA ’”‘‘–‡” ˆ”ƒ‰‡–• ˆ”‘ •‡˜‡ Aspergilli ”‡˜‡ƒŽ‡† ƒ Š‹‰ŠŽ› ‘•‡”˜‡† •‡“—‡ ‡ •–”‡– Š Œ—•–—’•–”‡ƒ‘ˆ–Š‡ͳǡ™Š‹ Šƒ›‹†‹ ƒ–‡ƒ„‹†‹‰•‹–‡ˆ‘”ƒ›‡–—‘™”‡‰—Žƒ–‘” ȋ ‹‰Ǥ ͳͲȌǤ

(43) –‡”‡•–‹‰Ž›ǡ –Š‡ „‘”†‡” ‘ˆ –Š‹• ‘•‡”˜‡† „‘š •Š‘™• •‡“—‡ ‡ •‹‹Žƒ”‹–› ™‹–Š –Š‡’ Ȁ Ͷ’„‹†‹‰•‹–‡ǡ ǡ™Š‹ Š ‘—Ž†„‡ Ž—‡–‘–Š‡‹˜‘Ž˜‡‡–‘ˆ’ ‹ –Š‡AspergillusǤ. Figure 10. Ž‹‰‡– ‘ˆ hacA ’”‘‘–‡” ˆ”ƒ‰‡–• ˆ”‘ •‡˜‡ AspergilliǤ Š‡ ‘•‡”˜‡† hacA ͳ „‘š ‹• —†‡”Ž‹‡†Ǥ ’•–”‡ƒ ‘ˆ –Š‡ ͳ ‹• ƒ‘–Š‡” ‘•‡”˜‡† •‡“—‡ ‡ •–”‡– ŠǤ Š‡ ’—–ƒ–‹˜‡’ „‹†‹‰•‹–‡‹•—†‡”Ž‹‡†Ǥ. GeneralDiscussion121.

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