Recent advances in heterologous production of natural products using <italic style="font-style: italic">Aspergillus oryzae</italic>

DONG Jiayu; LI Min; XIAO Zonghua; HU Ming; Yudai MATSUDA; WANG Weiguang

doi:10.12211/2096-8280.2022-007

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Recent advances in heterologous production of natural products using Aspergillus oryzae

Invited Review | 更新时间：2026-01-19

- Recent advances in heterologous production of natural products using Aspergillus oryzae
- Synthetic Biology Journal Vol. 3, Issue 6, Pages: 1126-1149(2022)
- 作者机构：
  
  1.云南民族大学，国家民委民族药内生菌天然产物合成生物学重点实验室，教育部国家民委民族药资源化学重点实验室，云南，昆明 650031
  2.香港城市大学化学系，香港 999077
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2022-007
  CLC： Q816
- Received：22 January 2022，
  
  Revised：2022-02-16，
  
  Published：31 December 2022
- 稿件说明：
移动端阅览
董佳钰，李敏，肖宗华，胡明，松田侑大，汪伟光. 米曲霉异源表达天然产物研究进展［J］. 合成生物学， 2022， 3（6）： 1126-1149

DONG Jiayu， LI Min， XIAO Zonghua， HU Ming， Yudai MATSUDA， WANG Weiguang. Recent advances in heterologous production of natural products using Aspergillus oryzae［J］. Synthetic Biology Journal， 2022， 3（6）： 1126-1149
董佳钰，李敏，肖宗华，胡明，松田侑大，汪伟光. 米曲霉异源表达天然产物研究进展［J］. 合成生物学， 2022， 3（6）： 1126-1149 DOI： 10.12211/2096-8280.2022-007.

DONG Jiayu， LI Min， XIAO Zonghua， HU Ming， Yudai MATSUDA， WANG Weiguang. Recent advances in heterologous production of natural products using Aspergillus oryzae［J］. Synthetic Biology Journal， 2022， 3（6）： 1126-1149 DOI： 10.12211/2096-8280.2022-007.

摘要

天然产物是创新药物和生物农药研发的重要源泉。阐明天然产物生物合成关键基因的功能、解析其生物合成通路和酶催化机制对于促进功能天然产物的应用和开发至关重要。异源表达是研究天然产物生物合成和合成生物学的重要手段之一。近年来，米曲霉异源宿主得到了广泛的应用。通过基因工程技术，将目的天然产物生物合成基因和基因簇在米曲霉中异源表达，不仅能够有效地激活沉默的生物合成基因和基因簇，挖掘全新活性天然产物，而且可以快速高效地鉴定天然产物生物合成基因功能，解析和重构其生物合成途径。米曲霉异源表达宿主已经成为天然产物合成生物学研究的强有力工具。本文对米曲霉遗传转化系统在天然产物研究中的应用进行了系统综述。首先，概述了异源表达的应用和意义，介绍了米曲霉遗传转化系统的发展过程、应用基础和优势以及遗传转化方法的实践和优化。其次，根据不同天然产物的结构类型和与之相对应的合成酶特点，着重介绍了该体系表达各类天然产物的成功案例。最后，对米曲霉异源表达宿主在天然产物化学领域的研究和应用前景进行了总结和展望。随着基因编辑、定向进化、合成生物学、生物信息学技术以及人工智能技术的发展和应用，米曲霉异源表达宿主的发展和完善将会极大地促进更多天然产物化学研究技术的发展和革新，以期为天然产物合成生物学的研究和创新药物研发提供借鉴。

Abstract

Organic molecules produced by living organisms

generally termed as natural products

are rich sources of pharmaceutical drugs and biopesticides

and fungi are one of the most prolific producers of medicinally important natural products

as represented by penicillins

lovastatin

and cyclosporins. Heterologous expression is a commonly used approach to study the function of biosynthetic genes of natural products

and a number of heterologous hosts have been developed and utilized over the last decades. The filamentous fungus

Aspergillus oryzae

has long been utilized for the production of fermented food and drinks in East Asia

and intensive genetic and molecular biological studies on the fungus have allowed for its genetic engineering in an efficient manner. Importantly

A. oryzae

is known to possess a relatively clean metabolic background with a low level of secondary metabolite production

providing an attractive feature as a heterologous host. Furthermore

unlike prokaryotic and yeast hosts

most coding sequences of fungal biosynthetic proteins can be directly introduced into

A. oryzae

in their intact form without removing introns

which simplifies the transformation procedures. Collectively

A. oryzae

is a robust platform for heterologous production of natural produc

which not only facilitates the elucidation of the biosynthetic pathway of a given natural product but also allows the activation of silent or cryptic biosynthetic gene clusters. Thus

the

A. oryzae

host has been widely utilized for biosynthetic studies

genome mining

and synthetic biology of fungal natural products. It should be noted that more than ten biosynthetic genes can readily be introduced into the fungus

indicating that the majority of fungal biosynthetic gene clusters can be easily transferred to the

A. oryzae

host. This review first provides the general transformation procedure of

A. oryzae

and the molecular biological tools available for the fungus. Next

recent successful applications of this fungal host for the heterologous production of natural products are summarized. With the recent rapid advance in molecular biology

such as the development of genome editing tools

we believe that the heterologous expression of biosynthetic genes in

A. oryzae

will be performed in a much faster and more versatile manner in the near future

which would ultimately lead to the discovery of useful natural products for drug leads and other applications.

关键词

Keywords

references

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Recent advances in heterologous production of natural products using Aspergillus oryzae

DOI：10.12211/2096-8280.2022-007

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